A proposed algorithm predictive for cytotoxic T cell alloreactivity

Previously, we showed that with an increasing number of amino acid differences in single HLA class I-mismatched molecules, the probability of T cell alloreactivity decreases. It is unlikely that every amino acid difference will affect T cell alloreactivity in a similar way; we hypothesized that the effect of an amino acid difference may be dependent on its position and/or physicochemical properties. We selected 131 patient/donor pairs with either a single HLA-A or -C mismatch in the graft-versus-host direction and that were compatible for HLA-B, -DRB1, and -DQB1. The alloreactive CTL precursor (CTLp) frequency was determined and associated with the amino acid differences between the single HLA class I mismatches. In the β sheet, only amino acids that are noncompatible in their physicochemical properties affect T cell alloreactivity, whereas in the α helices, both compatible and noncompatible amino acids affect CTLp outcome. Positions 62, 63, 73, 76, 77, 80, 99, 116, 138, 144, 147, and 163 were bivariately associated with CTLp outcome, irrespective of the total number of amino acid differences. In multivariate analysis, positions 62, 63, 73, 80, 116, 138, 144, and 163 were found to be most predictive for negative CTLp outcome. These results formed the basis for a weighted predictive mismatch score; pairs with the highest mismatch scores are estimated to be 13 times more likely to have a negative CTLp. This new algorithm may be a tool in donor selection for hematopoietic stem cell transplantation.     

Lying patterns of high producing healthy dairy cows after calving in commercial herds as affected by age,environmental conditions and production

An animal expresses its physiological and well-being status by its behaviour. Changes in behaviour can be associated with health, production or well-being problems and therefore with the profitability of the farm. The objectives of the present study were to analyse lying patterns of healthy cows, collected with a commercial behaviour sensor, in early lactation in relation to environmental conditions, age of the cow and production performance. In future, these results may be used as a ‘baseline’ for detection of alterations in behaviour that indicate health problems. The study involved 210 healthy multiparous Israeli Holstein cows in three commercial dairy farms. Only healthy cows during the first 28 days after calving were included in this study. Data were analysed in relation to calving season, age of cows and correlation between milk production and lying time.The results show that lying time increased significantly with age and is significantly (P < 0.05) higher in winter than in summer (summer lactation 2: 491 ± 17 min/day (mean ± SD), summer lactation 3 and more: 520 ± 25 min/day, winter lactation 2: 531 ± 25 min/day, winter lactation 3 and more: 579 ± 38 min/day).The proportion of positively and negatively milk production and lying time correlated cows is affected by calving season.This study indicates that behaviour variables in early lactation are affected by calving season, lactation number and type of correlation between milk production and lying time.     

Sexual imprinting can induce sexual preferences for exaggerated parental traits

Sexual preferences in animals are often skewed toward mates with exaggerated traits. In many vertebrates, parents provide, through the learning process of "sexual imprinting," the model for the later sexual preference. How imprinting can result in sexual preferences for mates having exaggerated traits rather than resembling the parental appearance is not clear. We test the hypothesis that a by-product of the learning process, "peak shift", may induce skewed sexual preferences for exaggerated parental phenotypes. To this end, zebra finch (Taeniopygia guttata) males were raised by white parents, with beak color as the most prominent sexual dimorphism. We manipulated this feature with nail varnish. At adult age, each male was given a preference test in which he could choose among eight females with beak colors ranging from more extreme on the paternal to more extreme on the maternal side. The males preferred females with a beak of a more extreme color than that of their mothers, i.e., they showed a peak shift. Sexual imprinting can thus generate skewed sexual preferences for exaggerated maternal phenotypes, phenotypes that have not been present at the time of the learning. We suggest that such preferences can drive the evolution of sexual dimorphism and exaggerated sexual traits.     

Cross-fostering Does Not Influence the Mate Preferences and Territorial Behaviour of Males in Lake Victoria Cichlids

The ability to recognise conspecifics in contexts of mate choice and territorial defence may have large effects on an individual's fitness. Understanding the development of assortative behaviour may shed light on how species assortative behaviour evolves and how it may influence reproductive isolation. This is the case not only for female mate preferences, but also for male mate preferences and male territorial behaviour. Here we test with a cross-fostering experiment whether early learning influences male mate preferences and male–male aggression biases in two closely related, sympatrically occurring cichlid species Pundamilia pundamilia and Pundamilia nyererei from Lake Victoria. Males that had been fostered, either by a conspecific female or by a heterospecific female, were tested for their aggression bias, as well as for their mate preferences, in two-way choice tests. Males cross-fostered with conspecific and heterospecific foster mothers selectively directed their aggression towards conspecific intruders. The cross-fostering treatment also did not affect male mate preferences. These results are in striking contrast with the finding that females of these species show a sexual preference for males of the foster species.     

Increased levels of (class switched) memory B cells in peripheral blood of current smokers

There is increasing evidence that a specific immune response contributes to the pathogenesis of COPD. B-cell follicles are present in lung tissue and increased anti-elastin titers have been found in plasma of COPD patients. Additionally, regulatory T cells (Tregs) have been implicated in its pathogenesis as they control immunological reactions. We hypothesize that the specific immune response in COPD is smoke induced, either by a direct effect of smoking or as a result of smoke-induced lung tissue destruction (i.e. formation of neo-epitopes or auto antigens). Furthermore, we propose that Tregs are involved in the suppression of this smoke-induced specific immune response.The presence of B cells, memory B cells and Tregs was assessed by flow cytometry in peripheral blood of 20 COPD patients and 29 healthy individuals and related to their current smoking status.COPD patients had lower (memory) B-cell percentages and higher Treg percentages in peripheral blood than healthy individuals, with a significant negative correlation between these cells. Interestingly, current smokers had higher percentages of (class-switched) memory B cells than ex-smokers and never smokers, irrespective of COPD.This increase in (class-switched) memory B cells in current smokers is intriguing and suggests that smoke-induced neo-antigens may be constantly induced in the lung. The negative correlation between B cells and Tregs in blood is in line with previously published observations that Tregs can suppress B cells. Future studies focusing on the presence of these (class switched) memory B cells in the lung, their antigen specificity and their interaction with Tregs are necessary to further elucidate the specific B-cell response in COPD.     

Induction of autoantibodies against lung matrix proteins and smoke-induced inflammation in mice

Background

Despite recommendations for outpatient management, low risk patients with lower respiratory tract infections (LRTIs) are often hospitalized. This survey analyzed perceptions of physicians, nurses, patients and relatives about feasibility of outpatient management and required duration of hospital stay.

Methods

We performed a prospective, observational questionnaire survey in hospitalized patients with LRTI as part of a multicenter trial. Treating physicians and nurses, patients and their relatives were asked on admission and before discharge about feasibility of outpatient treatment over 5 dimensions (medical, nursing, organizational factors, and patients' and relatives' preferences) using continuous scales.

Results

On admission, 12.6% of physicians, 15.1% of nurses, 18.0% of patients and 5.2% of relatives believed that outpatient treatment would be possible. Before hospital discharge, 31.1% of physicians, 32.2% of nurses, 11.6% of patients and 4.1% of relatives thought that earlier discharge would have been feasible. Medical factors were the most frequently perceived motives for inpatient management. These perceptions were similar in all LRTI subgroups and independent of disease severity and associated expected mortality risks as assessed by the Pneumonia Severity Index (PSI).

Conclusion

Independent of type and severity of respiratory tract infection, the misperceived high severity and expected mortality and morbidity were the predominant reasons why treating physicians, nurses, patients and their relatives unanimously believed that inpatient management was necessary. Better assessment and communication about true expected medical risks might contribute to a pathway to shorten in-hospital days and to introduce a more risk-targeted and individually tailored allocation of health-care resources.

Trial Registration

NCT00350987     

O-glucosylation of cis-zeatin in maize. Characterization of genes,enzymes, and endogenous cytokinins

trans-Zeatin is a major and ubiquitous cytokinin in higher plants. cis-Zeatin has traditionally been viewed as an adjunct with low activity and rare occurrence. Recent reports of cis-zeatin and its derivatives as the predominant cytokinin components in some plant tissues may call for a different perspective on cis-isomers. The existence of a maize (Zea mays) gene (cisZOG1) encoding an O-glucosyltransferase specific to cis-zeatin (R.C. Martin, M.C. Mok, J.E. Habben, D.W.S. Mok [2001] Proc Natl Acad Sci USA 98: 5922-5926) lends further support to this view. Results described here include the isolation of a second maize cisZOG gene, differential expression of cisZOG1 and cisZOG2, and identification of substantial amounts of cis-isomers in maize tissues. The open reading frame of cisZOG2 has 98.3% identity to cisZOG1 at the nucleotide level and 97.8% at the amino acid level. The upstream regions contain common and unique segments. The recombinant enzymes have similar properties, K(m) values of 46 and 96 microM, respectively, for cis-zeatin and a pH optimum of 7.5. Other cytokinins, including N(6)-(delta(2)-isopentenyl)adenine, trans-zeatin, benzyladenine, kinetin, and thidiazuron inhibited the reaction. Expression of cisZOG1 was high in maize roots and kernels, whereas cisZOG2 expression was high in roots but low in kernels. cis-Zeatin, cis-zeatin riboside, and their O-glucosides were detected in all maize tissues, with immature kernels containing very high levels of the O-glucoside of cis-zeatin riboside. The results are a clear indication that O-glucosylation of cis-zeatin is a natural metabolic process in maize. Whether cis-zeatin serves as a precursor to the active trans-isomer or has any other unique function remains to be demonstrated.     

Lygus rugulipennis on chrysanthemum: Supplemental prey effects and an evaluation of trap plants

The European tarnished plant bug, Lygus rugulipennis Poppius, is considered a major pest in chrysanthemum nurseries in The Netherlands. Adults puncture plant's apical meristem, after which the growing point splits and growth is inhibited. Flower buds and flowers can also be severely damaged. Both types of damage result in economic losses for growers. Despite the importance of this pest for chrysanthemum nurseries, there is only very limited information about L. rugulipennis development on chrysanthemum plants, Chrysanthemum × morifolium Ramat., and whether L. rugulipennis can be controlled using trap plants is not known. We investigated whether: (1) L. rugulipennis could develop from egg to adult on the vegetative and flowering stages of chrysanthemum; (2) their performance was enhanced when a supplemental prey source (Ephestia kuehniella Zeller eggs) or another common pest (the green peach aphid, Myzus persicae Sulzer) was present; and (3) there were alternative plant species more attractive than chrysanthemum for use as trap plants for local pest control or monitoring of L. rugulipennis. L. rugulipennis developed on both vegetative and flowering chrysanthemum stages without any additional food source. Nonetheless, when chrysanthemum was supplemented with E. kuehniella eggs, L. rugulipennis achieved the best performance in terms of the number of adults developed and faster developmental time. Interestingly, L. rugulipennis developed faster on chrysanthemum infested with the aphid M. persicae compared to non-infested plants, however, there was no difference in the number of adults developed. In a trap plant experiment with 16 plant species in the vegetative stage, we found that white mustard, Sinapis alba L., was significantly more attractive than chrysanthemum to both adult and nymph L. rugulipennis. Further research is needed to evaluate the potential of S. alba as a trap plant for monitoring L. rugulipennis and how the presence of prey in the crop influences L. rugulipennis.     

Default Mode Network Connectivity as a Function of Familial and Environmental Risk for Psychotic Disorder

Background

Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder.

Methods

Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology.

Results

There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity.

Discussion

Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network “connectivity at rest” intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.     

Malaria in the Post-Partum Period; a Prospective Cohort Study

Background

Several studies have shown a prolonged or increased susceptibility to malaria in the post-partum period. A matched cohort study was conducted to evaluate prospectively the susceptibility to malaria of post-partum women in an area where P.falciparum and P.vivax are prevalent.

Methods

In an area of low seasonal malaria transmission on the Thai-Myanmar border pregnant women attending antenatal clinics were matched to a non-pregnant, non-post-partum control and followed up prospectively until 12 weeks after delivery.

Results

Post-partum women (n = 744) experienced significantly less P.falciparum episodes than controls (hazard ratio (HR) 0.39 (95%CI 0.21–0.72) p = 0.003) but significantly more P.vivax (HR 1.34 (1.05–1.72) p = 0.018). The reduced risk of falciparum malaria was accounted for by reduced exposure, whereas a history of P.vivax infection during pregnancy was a strong risk factor for P.vivax in post-partum women (HR 13.98 (9.13–21.41), p<0.001). After controlling for effect modification by history of P.vivax, post-partum women were not more susceptible to P.vivax than controls (HR: 0.33 (0.21–0.51), p<0.001). Genotyping of pre-and post-partum infections (n⊕ = ⊕10) showed that each post-partum P.falciparum was a newly acquired infection.

Conclusions

In this area of low seasonal malaria transmission post-partum women were less likely to develop falciparum malaria but more likely to develop vivax malaria than controls. This was explained by reduced risk of exposure and increased risk of relapse, respectively. There was no evidence for altered susceptibility to malaria in the post-partum period. The treatment of vivax malaria during and immediately after pregnancy needs to be improved.