Type II arabinogalactans initiated by hydroxyproline-O-galactosyltransferases play important roles in pollen-pistil interactions.

Arabinogalactan-proteins (AGPs) are hydroxyproline-rich glycoproteins containing a high sugar content and are widely distributed in the plant kingdom. AGPs have long been suggested to play important roles in sexual plant reproduction. The synthesis of their complex carbohydrates is initiated by a family of hydroxyproline galactosyltransferase (Hyp-GALT) enzymes which add the first galactose to Hyp residues in the protein backbone. Eight Hyp-GALT enzymes have been identified so far, and in the present work a mutant affecting five of these enzymes (galt2galt5galt7galt8galt9) was analyzed regarding the reproductive process. The galt25789 mutant presented a low seed set, and reciprocal crosses indicated a significant female gametophytic contribution to this mutant phenotype. Mutant ovules revealed abnormal callose accumulation inside the embryo sac and integument defects at the micropylar region culminating in defects in pollen tube reception. In addition, immunolocalization and biochemical analyses allowed the detection of a reduction in the amount of glucuronic acid in mutant ovary AGPs. Dramatically low amounts of high-molecular-weight Hyp-O-glycosides obtained following size exclusion chromatography of base-hydrolyzed mutant AGPs compared to the wild type indicated the presence of underglycosylated AGPs in the galt25789 mutant, while the monosaccharide composition of these Hyp-O-glycosides displayed no significant changes compared to the wild-type Hyp-O-glycosides. The present work demonstrates the functional importance of the carbohydrate moieties of AGPs in ovule development and pollen-pistil interactions.

Is the link between the Dark Tetrad and the acceptance of sexual violence mediated by sexual machismo?

Previous studies have established relationships between the Dark Tetrad traits and sexual violence and its acceptance through myths about this type of violence. Sexual violence is positively associated with machismo, with sexist beliefs having been found to be linked with the Dark Tetrad and with the acceptance of sexual violence. Using a community sample comprising 362 adults between the ages of 18 and 70 (M = 35.6, SD = 14.3) and three self-report measures, this cross-sectional study aimed to explore the mediating role of sexual machismo in the relationship between each of the Dark Tetrad traits and the acceptance of sexual violence, both in the overall sample and by gender, as well as whether a significant variance in this acceptance is explained by the "dark" traits, sexual machismo, and gender. In the regression, sexual machismo (the male) gender, and only Machiavellianism were uniquely associated with the acceptance of sexual violence, and sexual machismo partially mediated the associations between the Dark Tetrad and the acceptance of sexual violence. These findings indicate that being male and higher in sexism is more closely linked with the acceptance of sexual violence than most Dark Tetrad traits. Moreover, the associations between the Dark Tetrad, sexual machismo, and the acceptance of sexual violence were stronger in men, consistent with the notion that these traits facilitate a "male" exploitive mating strategy, which likely also extends to victim-blaming and positive attitudes about sexual violence more broadly. Lastly, the results emphasize the pervasiveness of beliefs about male superiority over women and its relationship with victim-blaming even in women.

Intramacrophage lipid accumulation compromises T cell responses and is associated with impaired drug therapy against visceral leishmaniasis.

Under perturbing conditions such as infection with Leishmania, a protozoan parasite living within the phagosomes in mammalian macrophages, cellular and organellar structures, and metabolism are dynamically regulated for neutralizing the pressure of parasitism. However, how modulations of the host cell metabolic pathways support Leishmania infection remains unknown. Herein, we report that lipid accumulation heightens the susceptibility of mice to L. donovani infection and promotes resistance to first-line anti-leishmanial drugs. Despite being pro-inflammatory, the in vitro generated uninfected lipid-laden macrophages (LLMs) or adipose-tissue macrophages (ATMs) display lower levels of reactive oxygen and nitrogen species. Upon infection, LLMs secrete higher IL-10 and lower IL-12p70 cytokines, inhibiting CD4+ T cell activation and Th1 response suggesting a key modulatory role for intramacrophage lipid accumulation in anti-leishmanial host defence. We, therefore, examined this causal relationship between lipids and immunomodulation using an in vivo high-fat diet (HFD) mouse model. HFD increased the susceptibility to L. donovani infection accompanied by a defective CD4+ Th1 and CD8+ T cell response. The white adipose tissue of HFD mice displays increased susceptibility to L. donovani infection with the preferential infection of F4/80+ CD11b+ CD11c+ macrophages with higher levels of neutral lipids reserve. The HFD increased resistance to a first-line anti-leishmanial drug associated with a defective adaptive immune response. These data demonstrate that the accumulation of neutral lipids contributes to susceptibility to visceral leishmaniasis hindering host-protective immune response and reducing the efficacy of antiparasitic drug therapies.

AGPs as molecular determinants of reproductive development.

BACKGROUND AND AIMS: Morphogenesis occurs through accurate interaction between essential players to generate highly specialized plant organs. Fruit structure and function are triggered by a neat transcriptional control involving distinct regulator genes encoding transcription factors (TFs) or signalling proteins, such as the C2H2/C2HC zinc-finger NO TRANSMITTING TRACT (NTT) or the MADS-box protein SEEDSTICK (STK), which are important in setting plant reproductive competence, feasibly by affecting cell wall polysaccharide and lipid distribution. Arabinogalactan proteins (AGPs) are major components of the cell wall and are thought to be involved in the reproductive process as important players in specific stages of development. The detection of AGPs epitopes in reproductive tissues of NTT and other fruit development-related TFs, such as MADS-box proteins including SHATTERPROOF1 (SHP1), SHP2 and STK, was the focus of this study. METHODS: We used fluorescence microscopy to perform immunolocalization analyses on stk and ntt single mutants, on the ntt stk double mutant and on the stk shp1 shp2 triple mutant using specific anti-AGP monoclonal antibodies. In these mutants, the expression levels of selected AGP genes were also measured by quantitative real-time PCR and compared with the respective expression in wild-type (WT) plants. KEY RESULTS: The present immunolocalization study collects information on the distribution patterns of specific AGPs in Arabidopsis female reproductive tissues, complemented by the quantification of AGP expression levels, comparing WT, stk and ntt single mutants, the ntt stk double mutant and the stk shp1 shp2 triple mutant. CONCLUSIONS: These findings reveal distinct AGP distribution patterns in different developmental mutants related to the female reproductive unit in Arabidopsis. The value of the immunofluorescence labelling technique is highlighted in this study as an invaluable tool to dissect the remodelling nature of the cell wall in developmental processes.

The role of family doctors in the management of domestic violence cases - a qualitative study in Portugal.

BACKGROUND: Domestic violence leads to multiple health problems in victims and their families. Family doctors are in a particularly privileged position to detect, follow up, refer and report cases of domestic violence. However, little is known about the perception of these physicians regarding their role in managing domestic violence cases. METHODS: We conducted semi-structured interviews with family doctors from all regional health administrations of continental Portugal. Interviews were audio recorded, transcribed, and analysed using thematic analysis. RESULTS: Fifty-four family doctors participated in this study (n = 39 women, n = 15 men). The themes and subthemes that emerged from the data analysis translated doctors' broad responsibilities when approaching victims and aggressors. These included: "Implement preventive measures", "Empower the victim leading them to recognize the violent situation", "Detect domestic violence cases", "Treat health problems related to violence", "Provide emotional support", "Refer victims to specialized services", "Register the episode on the victims and/or aggressor clinical records", "Incentivize the victim to report", "Report the case to the authorities", "Intervene with the aggressor", "Protect other individuals" and "Follow up the patient and the process". CONCLUSIONS: The results of this study provide an overview of the current practical approaches being adopted by physicians and may provide a base for developing new interventions to support physicians to manage cases of domestic violence.

Risk Factors for Gambling Disorder: A Systematic Review.

Gambling disorder is a common and problematic behavioral disorder associated with depression, substance abuse, domestic violence, bankruptcy, and high suicide rates. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), pathological gambling was renamed "gambling disorder" and moved to the Substance-Related and Addiction Disorders chapter to acknowledge that research suggests that pathological gambling and alcohol and drug addiction are related. Therefore, this paper provides a systematic review of risk factors for gambling disorder. Systematic searches of EBSCO, PubMed, and Web of Science identified 33 records that met study inclusion criteria. A revised study acknowledges as risk factors for developing/maintaining a gambling disorder being a single young male, or married for less than 5 years, living alone, having a poor education, and struggling financially.

Method development and application to sediments for multi-residue analysis of organic contaminants using gas chromatography-tandem mass spectrometry.

A method for the determination of four classes of potentially toxic substances (PTSs) was developed and applied in marine sediments, including (i) polycyclic aromatic hydrocarbons (PAHs), (ii) polychlorinated biphenyls (PCBs), (iii) polybrominated diphenyl ethers (PBDEs), and (iv) organochlorinated pesticides (OCPs). The method is based on ultrasonic extraction with a mixture of dichloromethane:methanol (9:1 v/v) and gas chromatography coupled with tandem mass spectrometry analysis (GC-MS/MS) in multiple reaction monitoring (MRM) mode. A total of 89 compounds were identified using two precursor-product ion standards for each analyte. The method detection limit (MDL; 0.001-0.055 ng g-1 dw) and method quantification limit (MQL; 0.002-0.184 ng g-1 dw) are below the usual thresholds of pollution adopted by international sediment quality guidelines. The method proved to be selective, sensitive, accurate, and linear, with the advantage of reducing sample handling time and consumable expenses (solvent, adsorbents). The developed method was successfully applied to surface sediments of Sepetiba Bay, Rio de Janeiro State, Brazil. Total concentrations of PAH (29.20-209.5 ng g-1 dw), PCB (0.06-2.16 ng g-1 dw), OCP (0.03-0.33 ng g-1 dw), and PBDE (0.06-0.21 ng g-1 dw) represent a baseline for these compounds and revealed mild to low levels of contamination in comparison to other coastal bays in SE Brazil. By using the proposed method, we expect this preliminary dataset can be expanded and include other similar coastal systems from developing countries marked by scarcity of information about levels, risk assessment, and specific sediment quality guidelines encompassing multiple classes of regulated and emerging organic contaminants.

Psychological intervention with adult victims of sexual abuse: A comprehensive review.

Child sexual abuse (CSA) is a phenomenon that is ubiquitous to all cultures and social classes. It has short- and long-term consequences, with specific treatment models that have been developed and adapted from psychological intervention models. A wide variety of studies have sought to evaluate the results of treatments with adult CSA survivors. This study presents an overview of research on the treatment of adult victims of CSA, by reviewing the existing literature on the types of treatment and the most studied psychotherapeutic avenues, and reports the findings related to the efficacy of these treatments. It is possible to conclude that psychological intervention exhibits benefits in the reduction of symptoms resulting from the experience of CSA and demonstrates the need to conduct further research on the effectiveness of intervention.

Assessment of preschool-age executive functions: A systematic review.

Executive functions (EF) are higher-order cognitive processes present in the prefrontal cortex and are fundamental in planning, executing and monitoring goal-oriented behaviours. Evaluating EF in early stages of child development is essential for identifying any cognitive alterations in young children, given that it allows for early intervention and minimizes future complications. Additionally, it contributes to a better understanding of this construct in this age bracket, as well as its operational model. Study of EF has recently been the focus of multiple researchers; however, there is still a serious lack of instruments and measurements validated towards children's age bracket. This systematic review's main goal is to evaluate instruments and/or tasks that serve to evaluate and analyse EF and/or their components between the ages of 36 and 72 months. Forty-nine studies were analysed, containing multiple tasks and tools oriented towards EF and their constituent components. Results indicate the existence of various tasks that grade the different components independently from one another; nevertheless, they also confirm the lack of any global measurement instrument or method. Therefore, this systematic review presents itself as an important contribution in the study of EF, stressing not only the importance of further investing into constructing and validating new and better tools for evaluating the construct but also the study of operating models of executive functioning, especially in an age bracket where comprehending it is notoriously difficult.

Stem cell transplantation as treatment for major histocompatibility class I deficiency.

Major histocompatibility class I deficiency, due to genetic lesions in TAP1, TAP2, TAPBP, or B2M, manifests with recurrent sinopulmonary infections and granulomatous skin ulceration, and is predominately treated with antimicrobial prophylaxis and chest physiotherapy. One previous report of hematopoietic stem cell transplantation has been described in the literature, demonstrating cure of the immune defect without significant graft-versus-host disease. In this report, we expand the literature on HSCT in MHC-I deficiency with follow-up of the original patient, demonstrating maintained resolution of normal immune function and regression of the granulomatous rash 15 years post-transplant, and describe a further patient with mycobacterial disease whose transplant course was complicated by severe graft-versus-host disease.

Should domestic violence be or not a public crime?

BACKGROUND: Domestic violence has been addressed in public policies and law reforms in many countries to target its identification and provide increased support to those affected. In some countries, reporting domestic violence is mandatory, which means that anyone not only 'can' but also 'must' file a report, which is enough to progress the criminal proceedings, even against the victim's will. This article provides an overview about the importance of the clinicians' duty of care, debating whether or not domestic violence should be a public crime. METHODS: A narrative review on the subject of mandatory reporting of domestic violence, conducting a search of PubMed. RESULTS: Twenty studies were retrieved. Commonly victims agree with mandatory reporting. However, there are still several concerns voiced by both victims and health care workers that need to be further addressed. CONCLUSION: This article addresses the importance and limitations of mandatory reporting while acknowledging the impact of these measures in both the victim and the accused.

Paving the Way for Fertilization: The Role of the Transmitting Tract.

Angiosperm reproduction relies on the precise growth of the pollen tube through different pistil tissues carrying two sperm cells into the ovules' embryo sac, where they fuse with the egg and the central cell to accomplish double fertilization and ultimately initiate seed development. A network of intrinsic and tightly regulated communication and signaling cascades, which mediate continuous interactions between the pollen tube and the sporophytic and gametophytic female tissues, ensures the fast and meticulous growth of pollen tubes along the pistil, until it reaches the ovule embryo sac. Most of the pollen tube growth occurs in a specialized tissue-the transmitting tract-connecting the stigma, the style, and the ovary. This tissue is composed of highly secretory cells responsible for producing an extensive extracellular matrix. This multifaceted matrix is proposed to support and provide nutrition and adhesion for pollen tube growth and guidance. Insights pertaining to the mechanisms that underlie these processes remain sparse due to the difficulty of accessing and manipulating the female sporophytic tissues enclosed in the pistil. Here, we summarize the current knowledge on this key step of reproduction in flowering plants with special emphasis on the female transmitting tract tissue.

The best CRISPR/Cas9 versus RNA interference approaches for Arabinogalactan proteins' study.

Arabinogalactan Proteins (AGPs) are hydroxyproline-rich proteins containing a high proportion of carbohydrates, widely spread in the plant kingdom. AGPs have been suggested to play important roles in plant development processes, especially in sexual plant reproduction. Nevertheless, the functions of a large number of these molecules, remains to be discovered. In this review, we discuss two revolutionary genetic techniques that are able to decode the roles of these glycoproteins in an easy and efficient way. The RNA interference is a frequently technique used in plant biology that promotes genes silencing. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (CRISPR/Cas9), emerged a few years ago as a revolutionary genome-editing technique that has allowed null mutants to be obtained in a wide variety of organisms, including plants. The two techniques have some differences between them and depending on the research objective, these may work as advantage or disadvantage. In the present work, we propose the use of the two techniques to obtain AGP mutants easily and quickly, helping to unravel the role of AGPs, surely a great asset for the future.

Prognostic factors and clinical outcomes after stereotactic radiotherapy for primary lung tumors.

AIM: To characterize the population treated with SBRT for early-stage primary lung tumors in our institution, determine their outcomes, and identify potential prognosis factors. BACKGROUND: Stereotactic radiotherapy (SBRT) is an alternative treatment for inoperable patients with early-stage lung cancer. It confers a local control rate around 90% at 3 years, and 2-3 year overall survival rates of 43-60% in this population. MATERIALS AND METHODS: We retrospectively analyzed all patients treated in our department between 2012 and 2017 and evaluated local progression-free survival (L-PFS), nodal or distant progression-free survival (ND-PFS), global progression-free survival (G-PFS), overall survival (OS), and disease specific survival (DSS). Univariate (UVA) and multivariate (MVA) models were built to assess the influence of each variable. RESULTS: We identified 218 patients with 233 tumors. Most were male (78.9%) with a median age of 73 years. Median follow-up was 22 months. At 18 months, L-PFS was 93.7%, ND-PFS was 82.2%, G-PFS was 76.0%, DSS was 90.5%, and OS was 78.0% in ≤ T2 tumors. On UVA, T2 tumors were associated with lower L-PFS, G-PFS and DSS than T1, with no significant impact on ND-PFS or OS, an effect that persisted on MVA. On UVA, L-PFS and G-PFS were negatively influenced by female gender and a 5-fraction schedule was associated with worse G-PFS, which was not confirmed on MVA. CONCLUSION: Our local and distant control rates and survival were similar to those previously reported. On MVA, T2 tumors displayed lower L-PFS, G-PFS and DSS, with no difference in OS.

Insights into secrets along the pollen tube pathway in need to be discovered.

The process of plant fertilization provides an outstanding example of refined control of gene expression. During this elegant process, subtle communication occurs between neighboring cells, based on chemical signals, that induces cellular mechanisms of patterning and growth. Having faced an immediate issue of self-incompatibility responses, the pathway to fertilization starts once the stigmatic cells recognize a compatible pollen grain, and it continues with numerous players interacting to affect pollen tube growth and the puzzling process of navigation along the transmitting tract. The pollen tube goes through a guidance process that begins with a preovular stage (i.e. prior to the influence of the target ovule), with interactions with factors from the transmitting tissue. In the subsequent ovular-guidance stage a specific relationship develops between the pollen tube and its target ovule. This stage is divided into the funicular and micropylar guidance steps, with numerous receptors working in signalling cascades. Finally, just after the pollen tube has passed beyond the synergids, fusion of the gametes occurs and the developing seed-the ultimate aim of the process-will start to mature. In this paper, we review the existing knowledge of the crucial biological processes involved in pollen-pistil interactions that give rise to the new seed.

Autosomal recessive hyper-IgE syndrome successfully treated with hematopoietic stem cell transplantation.

Autosomal recessive hyper-IgE syndrome is a primary immunodeficiency that results from a mutation in the DOCK8 gene. We report a case of a patient presenting with severe eczema, atopy, and recurrent skin infections since the first months of life. The diagnosis of autosomal recessive hyper-IgE syndrome was made at the age of 7 by a positive DOCK8 genetic test. The patient underwent hematopoietic stem cell transplantation, with complete remission of the various manifestations.

Infection of hematopoietic stem cells by Leishmania infantum increases erythropoiesis and alters the phenotypic and functional profiles of progeny.

Immunosuppression is a well-established risk factor for Visceral Leishmaniasis. Post-immunosuppression leishmaniasis is characterized by an increase of parasite burden, hematopoietic disorders and unusual clinical manifestations. Although there are many reports on bone marrow findings in VL, less is known about the relationship between parasite dynamics in this organ and the function of either hematopoietic stem cells and progenitor cells themselves. In the present study, we tackle these issues using a new approach of infecting human stem cells derived from bone marrow with L. infantum. Using this strategy, we show that human hematopoietic stem cells (hHSC) are able to phagocytize L. infantum promastigotes and release modulatory and pro-inflammatory cytokines, mainly TNF-α. Our results demonstrated that L. infantum infection in vitro enhances hematopoiesis, favoring the development of erythrocitic lineage through a mechanism yet unknown. Moreover, we found that L. infantum infection alters the phenotypic profile of the hematopoietic progeny; modifying the surface markers expression of differentiated cells. Thus, our study represents a rare opportunity to monitor the in vitro differentiation of human stem cells experimentally infected by L. infantum to better understand the consequences of the infection on phenotypic and functional profile of the cell progeny.

The impact of IL-10 dynamic modulation on host immune response against visceral leishmaniasis.

Leishmaniasis is a vector-borne disease caused by protozoan parasites from the genus Leishmania. The most severe form of disease is visceral leishmaniasis (VL), which is fatal if left untreated. It has been demonstrated that interleukin (IL)-10, is associated with disease progression and susceptibility. In this work, we took advantage of a transgenic mouse model that expresses high levels of IL-10 upon zinc sulfate administration (pMT-10). We addressed the role of IL-10 during the initial stages of L. donovani infection by analyzing the parasite burden in the spleen and liver of the infected pMT-10 and WT mice as well as the histopathological alterations upon IL-10 induction. Furthermore, the profile of cytokines expressed by T cells was assessed. Our results demonstrate that an increase in IL-10 production has an impact early but not later after infection. This specific temporal role for IL-10-mediated susceptibility to VL is of interest.

Leishmania infantum modulates host macrophage mitochondrial metabolism by hijacking the SIRT1-AMPK axis.

Metabolic manipulation of host cells by intracellular pathogens is currently recognized to play an important role in the pathology of infection. Nevertheless, little information is available regarding mitochondrial energy metabolism in Leishmania infected macrophages. Here, we demonstrate that during L. infantum infection, macrophages switch from an early glycolytic metabolism to an oxidative phosphorylation, and this metabolic deviation requires SIRT1 and LKB1/AMPK. SIRT1 or LBK1 deficient macrophages infected with L. infantum failed to activate AMPK and up-regulate its targets such as Slc2a4 and Ppargc1a, which are essential for parasite growth. As a result, impairment of metabolic switch caused by SIRT1 or AMPK deficiency reduces parasite load in vitro and in vivo. Overall, our work demonstrates the importance of SIRT1 and AMPK energetic sensors for parasite intracellular survival and proliferation, highlighting the modulation of these proteins as potential therapeutic targets for the treatment of leishmaniasis.