DNA abrasion onto plants is an effective method for geminivirus infection and virus-induced gene silencing

Geminiviruses belong to a rapidly growing group of plant pathogens that contribute to crop losses in tropical and subtropical areas of the world. Geminivirus infection is a model for plant DNA replication and virus/host interactions. Geminiviruses are also used as vectors to induce silencing of endogenous genes in several plant species. A method was analyzed for inoculating geminiviruses using plasmid DNA rubbed onto leaves in the presence of an abrasive (DNA abrasion). Although the use of DNA abrasion to inoculate geminiviruses has been described previously, the technique has fallen out of favor and has not been systematically optimized. However, consistent efficiencies of 100% infection rates can be achieved by DNA abrasion. The symptoms of Tomato Golden Mosaic Virus or Cabbage Leaf Curl Virus infection on Nicotiana benthamiana were similar in timing and appearance to the symptoms observed in plants inoculated using Agrobacterium as the delivery method. More importantly, silencing of an endogenous gene was highly efficient when a geminivirus silencing vector was inoculated by the DNA abrasion method. Other plant species successfully inoculated with geminiviruses by DNA abrasion were Nicotiana tabacum, Capsicum annuum and Nicandra physalodes. Unfortunately, Arabidopsis thaliana could not be infected with Cabbage Leaf Curl Virus using leaf abrasion, demonstrating limitation of the method. However, leaf abrasion to inoculate geminiviruses is an easy and inexpensive method that should be considered as an accessible technique to the growing number of researchers using geminiviruses.     

Neurodevelopmental disorders: An innovative perspective via the response to intervention model

Neurodevelopmental disorders are a group of conditions classified together by the most recent edition of the Diagnostic and Statistical Manual of Mental Disorders which include intellectual disability, communication disorders, autism spectrum disorder, attention-deficit/hyperactivity disorder, specific learning disorder (SLD), and motor disorders. SLD is present in many students, who exhibit significant difficulties in the acquisition of reading, written expression, and mathematics, mostly due to problems with executive functions (EF). The present study is a review of the current situation of neurodevelopmental disorders and SLD focusing on the benefits of the response to intervention model (RtI), which allows the combination of evaluation and intervention processes. It also addresses the key role of EF. The importance of adapting RtI to new possibilities such as the use of virtual reality is discussed and a theoretical framework for carrying that out is provided.     

Association between Periodontal Disease and Inflammatory Arthritis Reveals Modulatory Functions by Melanocortin Receptor Type 3

Because there is clinical evidence for an association between periodontal disease and rheumatoid arthritis, it is important to develop suitable experimental models to explore pathogenic mechanisms and therapeutic opportunities. The K/BxN serum model of inflammatory arthritis was applied using distinct protocols, and modulation of joint disruption afforded by dexamethasone and calcitonin was established in comparison to the melanocortin (MC) receptor agonist DTrp⁸–γ-melanocyte stimulating hormone (MSH; DTrp). Wild-type and MC receptor type 3 (MC₃)-null mice of different ages were also used. There was significant association between severity of joint disease, induced with distinct protocols and volumes of the arthritogenic K/BxN serum, and periodontal bone damage. Therapeutic treatment with 10 μg dexamethasone, 30 ng elcatonin, and 20 μg DTrp per mouse revealed unique and distinctive pharmacological properties, with only DTrp protecting both joint and periodontal tissue. Further analyses in nonarthritic animals revealed higher susceptibility to periodontal bone loss in Mc3r^−/− compared with wild-type mice, with significant exacerbation at 14 weeks of age. These data reveal novel protective properties of endogenous MC₃ on periodontal status in health and disease and indicate that MC₃ activation could lead to the development of a new genus of anti-arthritic bone-sparing therapeutics.Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with progressive disability, early death, increased risk of cardiovascular events, and other extra-articular manifestations that have a major impact in the quality of life of those with the disease.^1,2 The current clinical approach is to start early, after diagnosis, with aggressive therapy, followed by treatment adjustments according to changes in disease activity. However, despite the important progress in RA therapies during the past decade, several needs are still unmet. The introduction of biological agents in the early 1990s revolutionized the treatment of RA and other chronic diseases, such as inflammatory bowel disease. However, although highly effective and generally faster acting than disease-modifying anti-rheumatic drugs, many patients are not responsive, and they may also experience an increased risk of opportunistic infections. The treatments are costly.³ Thus, there is justification for exploiting novel therapies. In addition, it is also desirable to produce new therapeutics with efficacy on pain and inflammation in the joint, but also able to temper systemic complications of RA affecting the heart, lungs, muscles, and bone.¹Targeting the melanocortin (MC) system⁴ to treat RA may represent an alternative opportunity to drug discovery.⁵ Indeed, one of the melanocortin agonists, adrenocorticotropin hormone (ACTH), was shown to be effective in human RA >60 years ago⁶; researchers are showing a renewed interest.⁷ This is prompted by the fact that ACTH may afford biological actions beyond the endogenous production of cortisol,^8,9 provoking activation of peripheral MC receptors, including the melanocortin receptor 3 (MC₃). This peripheral mechanism of action of ACTH, hence independent from adrenal release of glucocorticoids, might also underlie efficacy in conditions such as proteinuric nephropathies¹⁰ and multiple sclerosis.¹¹Surmounting evidence indicates an important counterregulatory role for the melanocortin pathway during inflammation, including in the osteo-articular system, where melanocortin receptors are expressed by osteoblasts, osteoclasts, chondrocytes, fibroblasts, and immune cells. Pharmacological targeting with MC peptides leads to a variety of protective actions, including increased matrix deposition, reduced fibroblast activation, and osteoblast and chondrocyte proliferation.^12–17 In vivo, the synthetic peptide DTrp⁸–γ-melanocyte stimulating hormone (MSH; DTrp) reduces clinical signs of disease in models of inflammatory arthritis¹⁸ and urate crystal peritonitis¹⁹ by a mechanism involving MC₃. In addition, the pan-MC agonist peptide AP214 also displays anti-arthritic properties.²⁰ Recent work by Gomez-SanMiguel et al²¹ reported that the MC agonist αMSH can reduce joint inflammation, together with an improvement of extra-articular signs associated with systemic arthritis, by increasing body weight and reducing levels of muscle-wasting markers.An important clinical manifestation associated with arthritis is periodontal disease. There is epidemiological evidence associating inflammation of the gum with incidence of RA²² and, conversely, there is a higher incidence of periodontitis in RA patients.²³ Intriguingly, recent reports demonstrated the presence of alveolar bone loss, an important feature of periodontitis, in rodents during the time course of experimental models of arthritis, namely collagen- and adjuvant-induced arthritis.^24–26 Herein, we investigated the presence of alveolar bone loss in a different model of experimental arthritis: one induced by the arthritogenic K/BxN serum, which is much faster in its kinetics, and is characterized by leukocyte infiltration, synoviocyte proliferation, and cartilage and bone erosion, thus resembling many features of human RA in its active flares.^27,28 In addition, we established the involvement of the melanocortin system in the development of alveolar bone loss by using a combination of genetically engineered mice and pharmacological approaches.     

Legal Status,Time in the USA,and the Well-Being of Latinos in Los Angeles

In the USA, undocumented Latino immigrants may have poorer health because of barriers to health care, stressors, and detrimental effects of immigration enforcement. Previous immigrant health research, however, suggests that recently arrived Latino immigrants have better health than US-born Latinos and their health deteriorates over time. Given the current environments that undocumented immigrants face, legal status is a structural factor that likely influences the patterns of immigrant health. Therefore, the aim of this study was to examine the extent to which physical and mental health differed by legal status and duration in the USA for the Latino population in Los Angeles County, California. We conducted analysis of Latino respondents (n = 1396) to the Los Angeles Family and Neighborhood Survey (L.A.FANS) Wave II. We examined self-reported health, depression measured by the Composite International Diagnostic Interview—Short Form, and blood pressure collected by trained interviewers. Respondents reported their legal status, time in the USA, and other sociodemographic characteristics. Regression models were used to test associations between each outcome and 1) legal status and 2) legal status by duration (≤ 15 and > 15 years) in the USA. Without taking duration into account, we found no significant differences in outcomes between undocumented, documented, or US-born Latinos. Taking duration into account, shorter duration undocumented immigrants had worse self-reported health than the US born. Undocumented immigrants, regardless of duration, had higher blood pressure than documented immigrants who had been in the USA for less time and the same level of blood pressure as the US born. In contrast, shorter duration documented immigrants had lower blood pressure compared to longer duration documented immigrants and US-born counterparts, and marginally lower blood pressure than shorter duration undocumented immigrants. The findings suggest that the “health advantage” generally presumed to exist among immigrants may not affect undocumented immigrants.     

Comparative analysis of clinical, biochemical and genetic aspects associated with bone mineral density in small for gestational age children

Clinical, biochemical and genetic analysis related to bone mineral density (BMD) were carried out in children born small for gestational age (SGA) that failed to achieve postnatal catch-up growth (CUG), SGA children that completed CUG and adequate for gestational age (AGA) children. Serum IGF-I, IGF-II, IGF binding protein-3 and acid-labile subunit were lower in the SGA-CUG children as compared with the other groups. Frequencies of polymorphic variants of vitamin D receptor, estrogen receptor and collagen genes were similar among groups. The genotype 194-192 of the IGF-I gene was higher in the SGA-CUG and 196-192 was higher in the SGA+CUG group. In the SGA-CUG group, the genotype SS of the COLIA1 gene was associated with lower BMD. Therefore, IGF system and COLIA1 polymorphism distinguish prepubertal SGA-CUG children from the SGA+CUG children of the same age. Furthermore, COLIA1 polymorphism could be useful to predict osteopenia in SGA-CUG children.     

About 1% of the breast and ovarian Spanish families testing negative for BRCA1 and BRCA2 are carriers of RAD51D pathogenic variants

RAD51D mutations have been recently identified in breast (BC) and ovarian cancer (OC) families. Although an etiological role in OC appears to be present, the association of RAD51D mutations and BC risk is more unclear. We aimed to determine the prevalence of germline RAD51D mutations in Spanish BC/OC families negative for BRCA1/BRCA2 mutations. We analyzed 842 index patients: 491 from BC/OC families, 171 BC families, 51 OC families and 129 patients without family history but with early‐onset BC or OC or metachronous BC and OC. Mutation detection was performed with high‐resolution melting, denaturing high‐performance liquid chromatography or Sanger sequencing. Three mutations were found in four families with BC and OC cases (0.82%). Two were novel: c.1A>T (p.Met1?) and c.667+2_667+23del, leading to the exon 7 skipping and one previously described: c.674C>T (p.Arg232*). All were present in BC/OC families with only one OC. The c.667+2_667+23del cosegregated in the family with one early‐onset BC and two bilateral BC cases. We also identified the c.629C>T (p.Ala210Val) variant, which was predicted in silico to be potentially pathogenic. About 1% of the BC and OC Spanish families negative for BRCA1/BRCA2 are carriers of RAD51D mutations. The presence of several BC mutation carriers, albeit in the context of familial OC, suggests an increased risk for BC, which should be taken into account in the follow‐up and early detection measures. RAD51D testing should be considered in clinical setting for families with BC and OC, irrespective of the number of OC cases in the family.