European Ancestry Predominates in Neuromyelitis Optica and Multiple Sclerosis Patients from Brazil

Background

Neuromyelitis optica (NMO) is considered relatively more common in non-Whites, whereas multiple sclerosis (MS) presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs) to estimate the genetic ancestry contribution to NMO patients.

Methods

Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP), Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP).

Principal Findings

European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7%) patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5%) patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population.

Conclusions

Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil.     

A critical role for dendritic cells in the formation of lymphatic vessels within tertiary lymphoid structures

Ectopic, or tertiary, lymphoid aggregates often form in chronically inflamed areas. Lymphatic vessels, as well as high endothelial venules, form within these lymphoid aggregates, but the mechanisms underlying their development are poorly understood. Overexpression of the chemokine CCL21 in the thyroid of transgenic mice leads to formation of lymphoid aggregates containing topologically segregated T and B lymphocytes, dendritic cells (DCs), and specialized vasculature, including Lyve-1(+)/Prox-1(+) lymphatic vessels. In this article, we show that adoptive transfer of mature CD4(+) T cells into animals expressing CCL21 in a RAG-deficient background promotes the influx of host NK cells and DCs into the thyroid and the formation of new lymphatic vessels within 10 d. This process is dependent on the expression of lymphotoxin ligands by host cells, but not by the transferred CD4(+) T cells. Ablation of host DCs, but not NK cells, reduces the formation of new lymphatic vessels in the thyroid. Taken together, these data suggest a critical role for CD11c(+) DCs in the induction of lymphangiogenesis in tertiary lymphoid structures.     

Effect of age and number of parturitions on uterine and ovarian variables in owl monkeys

Background We aimed to evaluate the uterine and ovarian volumes of owl monkeys in different age groups with different numbers of live births and to analyze the interaction between both. Methods We performed pelvic ultrasound exams to compare the uterine measurements with weight, age (infant, juvenile, subadult, young adults, and adults) and the number of live births (nulliparous, primiparous, and multiparous) and to compare the ovarian measurements with weight and age. Results and Conclusions The uterine volume (UV) was directly proportional to the number of parturitions, which was the most important factor in the uterine growth of adult females (P < 0.05). The body weight and age of the animals showed a high positive correlation with UV (r = 0.5354, r = 0.6489, P < 0.01), respectively. The volume of the ovaries grew in proportion to the age of the females (P < 0.05). Puberty was the period of greatest uterine and ovarian growth.     

Less Graft-Versus-Host Disease after Rabbit Antithymocyte Globulin Conditioning in Unrelated Bone Marrow Transplantation for Leukemia and Myelodysplasia: Comparison with Matched Related Bone Marrow Transplantation

One of the major drawbacks for unrelated donor (UD) bone marrow transplantation (BMT) is graft-versus-host disease (GVHD). Despite results from randomized trials, antithymocyte globulin (ATG) is not routinely included for GVHD prophylaxis in UD BMT by many centers. One of ways to demonstrate the usefulness of rabbit ATG in UD BMT is to evaluate how its results approximate to those observed in matched related (MRD) BMT. Therefore, we compared the outcomes between UD BMT with rabbit ATG (Thymoglobulin) for GVHD prophylaxis (n = 25) and MRD BMT (n = 91) for leukemia and myelodysplasia. All but one patient received a myeloablative conditioning regimen. Grades II–IV acute GVHD were similar (39.5% vs. 36%, p = 0.83); however, MRD BMT recipients developed more moderate-severe chronic GVHD (36.5% vs. 8.6%, p = 0.01) and GVHD-related deaths (32.5% vs. 5.6%, p = 0.04). UD BMT independently protected against chronic GVHD (hazard ratio 0.23, p = 0.04). The 6-month transplant-related mortality, 1-year relapse incidence, and 5-year survival rates were similar between patients with non-advanced disease in the MRD and UD BMT groups, 13.8% vs. 16.6% (p = 0.50), 20.8% vs. 16.6% (p = 0.37), and 57% vs. 50% (p = 0.67), respectively. Stable full donor chimerism was equally achieved (71.3% vs. 71.4%, p = 1). Incorporation of rabbit ATG in UD BMT promotes less GVHD, without jeopardizing chimerism evolution, and may attain similar survival outcomes as MRD BMT for leukemia and myelodysplasia especially in patients without advanced disease.     

Polyclonal antibody‐based ELISA in combination with specific PCR amplification of internal transcribed spacer regions for the detection and quantitation of Lasiodiplodia theobromae,causal agent of gummosis in cashew nut plants

Members of Botryosphaeriaceae family are associated with serious diseases in different plants across the world. In cashew nut plants (Anacardium occidentale), the fungus Lasiodiplodia theobromae causes a severe group of symptoms related to gummosis that results in decreased nut production. The aim of this work was to develop an indirect enzyme‐linked immunosorbent assay (ELISA) with sufficient sensitivity and specificity to detect the fungus both in vitro and in planta (artificially and naturally infected) and to increase the detection specificity within the fungi group using primers specific for the internal transcribed spacer (ITS) sequences. A collection of L. theobromae isolates was obtained, and antisera against the fungus were raised in rabbits. Cross‐reactivity against Neofusicoccum sp., Colletotrichum gloeosporioides, Phomopsis anacardii and Pestalotiopsis guepinii was examined. Naturally and artificially infected vegetal material were employed in the ELISAs. The fungi ITS sequences were determined, and single nucleotide polymorphisms were identified and used for primer design. For the naturally infected plants, there was an approximately fourfold variation in the absorbance values. Some positive readings for asymptomatic samples were detected. For the artificially infected samples, an ELISA‐based weekly time‐course analysis was conducted, and the values for samples from 0 and 7 days were lower than the threshold value. Beginning on day 14, the infection could be detected, with rates varying from 40% on day 14 to 80% on day 21 and 100% by the end of the experiment. The ITS sequencing revealed few polymorphisms among the L. theobromae isolates, but for C. gloeosporioides, P. anacardii, P. guepinii and Neofusicoccum sp., the sequences were sufficient to permit reliable discrimination. The feasibility of ELISA as an early detection technique to assist in gummosis management was demonstrated. PCR amplification based on ITS regions increases and complements serological specificity.     

Do males time their mate-guarding effort with the fertile phase in order to secure fertilisation in Cayo Santiago rhesus macaques?

In contrast to most mammalian species, female sexual activity is not limited to the fertile phase of the ovarian cycle in anthropoid primates, which has long been proposed to conceal the timing of ovulation to males. It is now generally believed that females are still most attractive during the fertile phase, leading to high-ranking males successfully mate-guarding them specifically during this period. While studies conducted in species exhibiting exaggerated sexual swellings (probabilistic signal of the fertile phase) have generally supported this hypothesis, mixed support comes from others. Here, we investigated whether high-ranking males timed mate-guarding effort towards female fertile phases in rhesus macaques (Macaca mulatta). In this species, adult females do not exhibit sexual swellings, but undergo facial skin colour variation, an alternative oestrogen-dependent graded-signal of female reproductive status. We collected behavioural, hormonal and genetic paternity data during two mating seasons for one group of the free-ranging population of Cayo Santiago. Our results show that mate-guarding by top-ranking males did not completely cover the entire female fertile phase and that this tactic accounted for only 30-40% of all fertilisations observed. Males tended to prolong mate-guarding into the luteal phase (null probability of fertilisation), which mirrors the pattern of male attraction to female facial colour reported in an earlier study. These findings suggest that males may have limited knowledge regarding the exact timing of females' fertile phase in rhesus macaques, which presumably allows females to gain more control over reproduction relative to other anthropoid primate species.