Search

We have developed a single-tube multiplex real-time PCR method for the detection of the eight most common Candida species causing septicemia: Candida albicans , C. dubliniensis , C. famata , C. glabrata , C. guilliermondii , C. krusei , C. parapsilosis , and C. tropicalis . The method developed targets the RNase P RNA gene RPR1 . Sequences of this gene were determined for seven of the Candida species and showed surprisingly large sequence variation. C. glabrata was found to have a gene that was five times longer gene than those of the other species, and the nucleotide sequence similarity between C. krusei and C. albicans was as low as 55%. The multiplex PCR contained three probes that enabled the specific detection of C. albicans , C. glabrata , and C. krusei and a fourth probe that allowed the general detection of the remaining species. The method was able to detect 1 to 10 genome copies when the detection limit was tested repeatedly for the four species C. albicans , C. glabrata , C. krusei , and C. guilliermondii . No significant difference in the detection limit was seen when the multiplex format was compared with single-species PCR, i.e., two primers and one probe. The method detected eight clinically relevant Candida species and did not react with other tested non- Candida species or human DNA. The assay was applied to 20 blood samples from nine patients and showed a sensitivity similar to that of culture.

The current shift from phenotypically toward genotypically based microbial diagnosis is not unproblematic. A novel quantitative real-time polymerase chain reaction (PCR) assay based on the Spn9802 DNA fragment was therefore developed for detection of Streptococcus pneumoniae. Out of 44 bacterial species, only S. pneumoniae and Streptococcus pseudopneumoniae were positive in Spn9802 PCR. In an evaluation on nasopharyngeal aspirates from 166 patients with community-acquired pneumonia, the assay was positive in 49 of 50 culture-positive cases. Of 19 culture-negative but Spn9802 PCR-positive cases, 12 were confirmed as S. pneumoniae by rnpB sequence analysis. With an expanded reference standard, including culture and rnpB sequencing, Spn9802 had a sensitivity of 94% and a specificity of 98%. A cutoff for clinically significant positivity was 10(4) DNA copies/mL, giving 71% sensitivity and 100% specificity. In conclusion, Spn9802 real-time PCR is highly sensitive and specific. The quantification it provides enables differentiation between pneumococcal pathogenicity and commensalism.

We present an extensive analysis of squark and gaugino hadroproduction and decays in non-minimal flavour violating supersymmetry. We employ the so-called super-CKM basis to define the possible misalignment of quark and squark rotations, and we use generalized (possibly complex) charges to define the mutual couplings of (s)quarks and gauge bosons/gauginos. The cross sections for all squark-(anti-)squark/gaugino pair and squark-gaugino associated production processes as well as their decay widths are then given in compact analytic form. For four different constrained supersymmetry breaking models with non-minimal flavour violation in the second/third generation squark sector only, we establish the parameter space regions allowed/favoured by low-energy, electroweak precision, and cosmological constraints and display the chirality and flavour decomposition of all up- and down-type squark mass eigenstates. Finally, we compute numerically the dependence of a representative sample of production cross sections at the LHC on the off-diagonal mass matrix elements in the experimentally allowed/favoured ranges., Comment: 35 pages, 29 (partly colour) figures. Some typos corrected, wording of several paragraphs improved, version accepted by Nucl. Phys. B

In the Swedish county of Halland, it was recently reported that a proportion of sexually transmitted Chlamydia trachomatis infections could not be detected using standard laboratory tests manufactured by Abbott and Roche

Two cases of the sexually transmitted infection lymphogranuloma venereum (LGV) were detected in men who have sex with men (MSM) in Sweden during 2004

Patients with Autoimmune polyendocrine syndrome type I (APS I) present with multiple endocrine failures due to organ-specific autoimmune disease, thought to be T-cell-mediated. Paradoxically, APS I patients suffer from chronic mucocutaneous candidiasis. The mutated gene has been identified as the Autoimmune regulator (AIRE). Aire is expressed in medullary epithelial cells of the thymus and in antigen presenting cells in the periphery. T cells from Aire deficient mice and men displayed an enhanced proliferative response against Candida antigen in vitro, suggesting that Aire deficient T cells are competent in recognizing Candida albicans. In contrast, monocytes from APS I patients displayed a decreased and delayed internalization of zymosan. Furthermore, Candida antigen activated monocytes from APS I patients show decreased and altered phoshotyrosine kinase activation. In conclusion, Aire deficient APCs have a defect receptor mediated internalization of Candida which affects kinase activation, likely altering the innate Candida immune response.

The rnpB gene is ubiquitous in Bacteria, Archaea and Eucarya and encodes the RNA component of RNase P, an endoribonuclease P that consists of one RNA and one protein subunit (C5). In this study, partial rnpB genes were sequenced from 39 type strains and 16 additional strains of the genus Legionella. Models of the putative secondary structures of the RNase P RNA in the genus Legionella are proposed and possible interactions between RNase P RNA and C5 are discussed. The phylogenetic relationships within the genus Legionella were examined and rnpB sequences indicated six main clades that together comprised 27 of the 39 species examined. The phylogenetic relationships were further inferred by analysing combined datasets of sequences from the rnpB, mip, 16S rRNA and rpoB genes. It is concluded that rnpB is suitable for use in phylogenetic studies of closely related species and that it exhibits the potential to discriminate between Legionella species.

In this study we aimed to characterize the ompA gene by sequencing DNA from all detected cases of Chlamydia trachomatis infection in a Swedish county during 2001, in order to improve the efficiency of contact tracing. Approximately 990 bp of the ompA gene was amplified, and sequence analysis was achieved in 678 (94%) of 725 C. trachomatis -positive cases in this unselected population. The most prevalent genotype was serotype E (39%), followed by F (21%), G (11%), D (9%), K (9%), J (7%), H (2%), B (1%), and Ia (1%). Serotype E was found in five genotype variants, with the reference sequence comprising 96% of all E cases. Serotype D was the most variable, and of seven sequence variants, three were identified as recombinants with serotype E. Altogether 29 genetic variants were detected, and mutations and recombination events are discussed. Clinical manifestations were not associated with genotypes. Sequence variation was linked to sexual networks identified by contact tracing and improved epidemiological knowledge but was of limited benefit.

Respiratory syncytial virus (RSV) and chlamydial infection may be pathogenetic factors in allergic diseases, perhaps also in ocular allergy. We analyzed the presence of RSV and chlamydial nucleic acids using reverse transcription (RT)-PCR and PCR, respectively, in conjunctival biopsies from patients with vernal keratoconjunctivitis (VKC) in order to determine whether these agents play a role in the maintenance of the disease. All biopsy samples were negative for both RSV (n = 15 for VKC and n = 10 for control subjects) and chlamydia (n = 8 for VKC and n = 7 for control subjects) homologous sequences. A direct association between RSV or chlamydial infection and ongoing inflammation in VKC could, therefore, not be confirmed.

Our objectives were to compare the prevalence of sexually transmitted infections (STIs) in 103 women undergoing induced legal abortion (LA) and in 101 women with confirmed, recent illegal abortion (IA), in Maputo, Mozambique. For the purpose of this study, LA was considered the abortion provided in the Maputo Central Hospital with the approval of the Ministry of Health, and IA the one not provided through the approved facility, mentioned above. Women with IA were recruited in the outpatient gynaecology ward and women with LA in the emergency gynaecology ward in the Maputo Central Hospital, during the same time period. Serological tests for syphilis (rapid plasma reagin, ELISA-IgG and fluorescent treponemal antibody absorption), gonorrhoea (indirect haemagglutination) and chlamydia (microimmunofluorescence) were carried out. Direct immunofluorescence for detection of Chlamydia trachomatis antigen was done on endocervical smears from all the women. The prevalence of syphilis seropositivity in IA women is twice that of LA women (odds ratio [OR] 2.13; 95% confidence interval [CI] 0.55-9.95), with 10.9% and 4.9%, respectively. Exposure to gonorrhoea in these 2 groups is similar (OR 1.18; 95% CI 0.63-2.20), with seroprevalence of 31.1% in the LA and 34.7% in the IA group. The high titres are also similar in both groups. Serology findings for C. trachomatis indicate prevalence of seropositivity of 40.6% in the LA and 44.4% in the IA group with no significant difference (OR 1.17; 95% CI 0.64-2.13). In conclusion, STIs are highly prevalent in both IA and LA groups in Maputo. Urgent interventions are needed to reduce their prevalence and consequently their adverse consequences.

A nested reverse transcription (RT)-PCR was developed for simultaneous detection and typing of influenza viruses A and B. The detection limit for influenza virus A subtypes H1 and H3 and that for influenza virus B were between 1 and 4 target gene copies per reaction for each type. The clinical benefit of the RT-PCR method was evaluated by comparing the results with virus isolation and direct immunofluorescence (IF) assays on 215 nasopharyngeal aspirates from patients with suspected influenza virus infection. The RT-PCR detected 83 cases of influenza A, compared to 66 cases detected by virus isolation and 68 cases detected by IF assay. The corresponding figures for the detection of influenza B were 15, 12, and 11 cases, respectively. In total, 16 out of 98 RT-PCR-positive specimens were negative by virus isolation and IF. An optical immunoassay for rapid detection of influenza A and B (FLU OIA; Bio Star Inc., Boulder, Colo.) was compared to RT-PCR and IF on 105 nasopharyngeal aspirates and 79 swabs. The sensitivity for the OIA was 40.4% compared to PCR and 48.8% compared to IF assay, when nasopharyngeal aspirates were examined. The specificities were 94.3 and 93.9%, respectively. The sensitivity was higher for OIA on nasopharyngeal swabs, 77.5% and 86.6% compared to PCR and IF, respectively, while the specificity was lower, 82.0% and 75.5%, respectively. The RT-PCR provides a sensitive and specific method for detecting and typing influenza viruses A and B. The rapid OIA is useful as a complementary test, but it cannot replace established methods without further evaluation.

On Bird Island, South Georgia, a new strain of Chlamydophila abortus was detected in one Brown skua out of 37 specimens from six different seabird species. Phylogenetic analysis of the rnpB and omp1 genes indicated the strain to be more closely related to C. abortus than to 6BC, the type strain of Chlamydophila psittaci .

The sequence of the RNase P RNA gene (rnpB) was determined for 60 strains representing all nine species in the family Chlamydiaceae and for the related Chlamydiales species, Parachlamydia acanthamoebae and Simkania negevensis. These sequences were used to infer evolutionary relationships among the Chlamydiaceae. The analysis separated Chlamydophila and Chlamydia into two lineages, with Chlamydophila forming three distinct clusters: the Chlamydophila pneumoniae strains; the Chlamydophila pecorum strains; and a third cluster comprising the species Chlamydophila psittaci, Chlamydophila abortus, Chlamydophila caviae and Chlamydophila felis. The Chlamydia line of descent contained two clusters, with the Chlamydia suis strains distinctly separated from strains of Chlamydia trachomatis and Chlamydia muridarum. This analysis indicated that the rnpB sequence and structure are distinctive markers for species in the Chlamydiaceae. It was also demonstrated that the RNase P RNA derived from Chlamydia trachomatis is able to cleave a tRNA precursor in the absence of protein. These findings are discussed in relation to the structure of Chlamydia RNase P RNA.

Contrasting trends in rates of genital chlamydial infection and ectopic pregnancy in South East Thames Region, England and Uppsala County, Sweden: ecological study

Background The Chlamydia trachomatis MLST database was established in 2007 and is based on five target regions (non-housekeeping genes) and the conventional ompA gene. It enables worldwide epidemiological analyses. Methods Samples were included from 11 studies focusing on specific risk groups and with different study objectives. Geographical distribution of MLST profiles was carried out and eBURST analysis identified genetic founders. Results A total of 414 MLST profiles were recognised from 2087 entries. Polymorphism of target regions was reflected in varying numbers of alleles; hctB 89, CT058 51, CT144 30, CT172 41, pbpB 35. With addition of 49 ompA gene variants 459 profiles exist. There were 16 countries from which samples originated, the majority coming from the Netherlands 39%, Sweden 16% and Norway 12%, but also samples from countries in North and South America, Africa and other European countries. Overall 605 (29%) of the database samples originated from men having sex with men (MSM) while the remaining samples were assumed to be from heterosexuals. Singletons or small clusters emerged from 377 of the MLST profiles that were found 1–9 times while 31 profiles were found 10–43 times each. There were 8 profiles that predominated and were each found between 83 and 140 times and constituted large clusters that comprised 868 samples (41.6%). Four of the predominating profiles were strongly associated with MSM, with 96 – 100% of the samples coming from MSM. In the other four large clusters heterosexuals comprised > 90% of the samples. eBURST analysis identified 3 of the 8 predominating profiles as founders, and another 3 as subgroup founders. The genetic diversity was much lower in the MSM clusters compared to clusters in heterosexuals. Conclusions Worldwide a few C. trachomatis MLST profiles predominate. Different MLST profiles predominate among MSM and heterosexuals.

Background The first case of LGV in Barcelona was diagnosed in 2005 and since then around 200 cases have been notified up to 2012. All cases have been diagnosed among MSM, 80% of them coinfected with HIV and 97% of the cases had proctitis. Since 2008 some cases have appeared with extrarectal manifestations. Objective To compare the molecular epidemiology profiles of extrarectal LGV cases diagnosed in Barcelona with profiles reported in rectal cases. Methods A convenient 14 samples from 9 confirmed LGV cases in 2012 with extrarectal involvement were selected for LGV typing. DNA was extracted from samples using a semi automated system and kept al –80o C. The strains were further analysed by genotyping using a multilocus sequence typing (MLST) based on 5 highly variable gene regions, in addition the ompA gene was sequenced. Results DNA quality for MLST was suboptimal in some samples. The genotyping pattern showed one single MLST-5 profile (27, 13, 17, 13, 28) among all the samples. In ompA there were two variants (22 and 28), in the 2 cases with ompA variant 22 the samples were obtained from inguinal ganglia. Discussion The MLST-5 profile in LGV cases from Barcelona is the same as the predominating sequence type found in rectal cases. This is in line with the spread of a single clone, without specific tissue tropism. In ompA the 2 cases with variant 22 were identical to ompA in the reference strain L2/434/Bu, but differed from the currently predominating variant L2b among MSM. Considering the difference in ompA is minor it is more probable that L2b is a classical L2 isolate that has been circulating for a long time but showing now a new spectrum of manifestations. Our study does not support any difference in LGV strains obtained from extrarectal sites or from rectum.

Background The histone-like protein Hc2 binds DNA in Chlamydia trachomatis and is known to vary in size between 165 and 237 amino acids, which is caused by different numbers of lysine-rich pentamers. A more complex structure was seen in this study when sequences from 378 specimens covering the hctB gene, which encodes Hc2, were compared. Results This study shows that the size variation is due to different numbers of 36-amino acid long repetitive elements built up of five pentamers and one hexamer. Deletions and amino acid substitutions result in 14 variants of repetitive elements and these elements are combined into 22 configurations. A protein with similar structure has been described in Bordetella but was now also found in other genera, including Burkholderia, Herminiimonas, Minibacterium and Ralstonia. Sequence determination resulted in 41 hctB variants that formed four clades in phylogenetic analysis. Strains causing the eye disease trachoma and strains causing invasive lymphogranuloma venereum infections formed separate clades, while strains from urogenital infections were more heterogeneous. Three cases of recombination were identified. The size variation of Hc2 has previously been attributed to deletions of pentamers but we show that the structure is more complex with both duplication and deletions of 36-amino acid long elements. Conclusions The polymorphisms in Hc2 need to be further investigated in experimental studies since DNA binding is essential for the unique biphasic life cycle of the Chlamydiacae. The high sequence variation in the corresponding hctB gene enables phylogenetic analysis and provides a suitable target for the genotyping of C. trachomatis.

Diagnostic work on the detection of Chlamydia trachomatis infections in Uppsala county, Sweden, during the period from April 1985 to March 1991 was studied. The number of patients examined for C. trachomatis in this area increased annually by 6% to 15% during the study period, reaching 17,224 test occasions by the last 12-month period. A 40% decrease (from 1,412 to 852; or from 565 to 326 cases per 100,000 inhabitants) in diagnosed C. trachomatis infections was noted between the first and the last 12-month period. No significant tendencies were evident in either age distribution or sex ratio in the detected cases during the study period. Intensified sampling work was noted at youth clinics and maternal health care centers, while the dominant role of the venereal disease clinic as case detector declined steadily. The results have been interpreted in the context of available national figures for Sweden.

In 2006, a new variant of Chlamydia trachomatis (nvCT) was discovered in Sweden that was not detectable with Abbott m2000 (Abbott) and Amplicor/COBAS Amplicor/TaqMan48 (Roche). The proportion of nvCT was 20–64% of the detected Chlamydia cases in counties using Abbott/Roche test systems. Although the ProbeTec system from Becton Dickinson (BD) could detect nvCT, the proportion of nvCT in counties using BD was 7–19%. The objective of the current study was to follow the nvCT proportions from 2007 to 2009 in two counties that used Roche and had introduced test systems able to detect nvCT in late 2006. The nvCT was also followed in two counties that used BD, and in all four counties the effect of nvCT on the serotype distribution of C. trachomatis wild‐type strains was analysed. A total of 2576 specimens positive for C. trachomatis were collected in the four counties at three time points, and analysed for nvCT and serotype E. The proportion of nvCT declined significantly in the two counties using Roche, from 65% and 48% in 2007 to 24% for both counties in 2009 (p

The pneumolysin (ply) gene is widely used as a target in PCR assays for Streptococcus pneumoniae in respiratory secretions. However, false-positive results with conventional ply-based PCR have been reported. The aim here was to study the performance of a quantitative ply-based PCR for the identification of pneumococcal lower respiratory tract infection (LRTI). In a prospective study, fibreoptic bronchoscopy was performed in 156 hospitalized adult patients with LRTI and 31 controls who underwent bronchoscopy because of suspicion of malignancy. Among the LRTI patients and controls, the quantitative ply-based PCR applied to bronchoalveolar lavage (BAL) fluid was positive ator=10(3) genome copies/mL in 61% and 71% of the subjects, ator=10(5) genome copies/mL in 40% and 58% of the subjects, and ator=10(7) genome copies/mL in 15% and 3.2% of the subjects, respectively. Using BAL fluid culture, blood culture, and/or a urinary antigen test, S. pneumoniae was identified in 19 LRTI patients. As compared with these diagnostic methods used in combination, quantitative ply-based PCR showed sensitivities and specificities of 89% and 43% at a cut-off of 10(3) genome copies/mL, of 84% and 66% at a cut-off of 10(5) genome copies/mL, and of 53% and 90% at a cut-off of 10(7) genome copies/mL, respectively. In conclusion, a high cut-off with the quantitative ply-based PCR was required to reach acceptable specificity. However, as a high cut-off resulted in low sensitivity, quantitative ply-based PCR does not appear to be clinically useful. Quantitative PCR methods for S. pneumoniae using alternative gene targets should be evaluated.

Catabacter hongkongensis was isolated and cultured from human blood for the first time in Scandinavia. The patient, an 83-year-old man from Dalarna, Sweden, recovered without antibiotic treatment, although a high mortality rate associated with C. hongkongensis infection had been reported from China, Canada and France. The genome of the strain ABBA15k was sequenced, assembled and analysed. In contrast to the type strain of the species HKU16T, no antibiotic resistance was observed in Scandinavian strain ABBA15k. The strain was deposited as CCUG 68271, and the draft genome sequence is available from the DNA Data Bank of Japan (DDBJ), the European Molecular Biology Laboratory (EMBL), and GenBank under the accession number LLYX00000000.

Our sensory environment is teeming with complex rhythmic structure, to which neural oscillations can become synchronized. Neural synchronization to environmental rhythms (entrainment) is hypothesized to shape human perception, as rhythmic structure acts to temporally organize cortical excitability. In the current human electroencephalography study, we investigated how behavior is influenced by neural oscillatory dynamics when the rhythmic fluctuations in the sensory environment take on a naturalistic degree of complexity. Listeners detected near-threshold gaps in auditory stimuli that were simultaneously modulated in frequency (frequency modulation, 3.1 Hz) and amplitude (amplitude modulation, 5.075 Hz); modulation rates and types were chosen to mimic the complex rhythmic structure of natural speech. Neural oscillations were entrained by both the frequency modulation and amplitude modulation in the stimulation. Critically, listeners' target-detection accuracy depended on the specific phase-phase relationship between entrained neural oscillations in both the 3.1-Hz and 5.075-Hz frequency bands, with the best performance occurring when the respective troughs in both neural oscillations coincided. Neural-phase effects were specific to the frequency bands entrained by the rhythmic stimulation. Moreover, the degree of behavioral comodulation by neural phase in both frequency bands exceeded the degree of behavioral modulation by either frequency band alone. Our results elucidate how fluctuating excitability, within and across multiple entrained frequency bands, shapes the effective neural processing of environmental stimuli. More generally, the frequency-specific nature of behavioral comodulation effects suggests that environmental rhythms act to reduce the complexity of high-dimensional neural states.

Stimulus-specific adaptation refers to a neural response reduction to a repeated stimulus that does not generalize to other stimuli. However, stimulus-specific adaptation appears to be influenced by additional factors. For example, the statistical distribution of tone frequencies has recently been shown to dynamically alter stimulus-specific adaptation in human auditory cortex. The present study investigated whether statistical stimulus distributions also affect stimulus-specific adaptation at an earlier stage of the auditory hierarchy. Neural spiking activity and local field potentials were recorded from inferior colliculus neurons of rats while tones were presented in oddball sequences that formed two different statistical contexts. Each sequence consisted of a repeatedly presented tone (standard) and three rare deviants of different magnitudes (small, moderate, large spectral change). The critical manipulation was the relative probability with which large spectral changes occurred. In one context the probability was high (relative to all deviants), while it was low in the other context. We observed larger responses for deviants compared with standards, confirming previous reports of increased response adaptation for frequently presented tones. Importantly, the statistical context in which tones were presented strongly modulated stimulus-specific adaptation. Physically and probabilistically identical stimuli (moderate deviants) in the two statistical contexts elicited different response magnitudes consistent with neural gain changes and thus neural sensitivity adjustments induced by the spectral range of a stimulus distribution. The data show that already at the level of the inferior colliculus stimulus-specific adaptation is dynamically altered by the statistical context in which stimuli occur.

Speech comprehension in multitalker situations is a notorious real-life challenge, particularly for older listeners. Younger listeners exploit stimulus-inherent acoustic detail, but are they also actively predicting upcoming information? And further, how do older listeners deal with acoustic and predictive information? To understand the neural dynamics of listening difficulties and according listening strategies, we contrasted neural responses in the alpha-band (∼10 Hz) in younger (20–30 years,n= 18) and healthy older (60–70 years,n= 20) participants under changing task demands in a two-talker paradigm. Electroencephalograms were recorded while humans listened to two spoken digits against a distracting talker and decided whether the second digit was smaller or larger. Acoustic detail (temporal fine structure) and predictiveness (the degree to which the first digit predicted the second) varied orthogonally. Alpha power at widespread scalp sites decreased with increasing acoustic detail (during target digit presentation) but also with increasing predictiveness (in-between target digits). For older compared with younger listeners, acoustic detail had a stronger impact on task performance and alpha power modulation. This suggests that alpha dynamics plays an important role in the changes in listening behavior that occur with age. Last, alpha power variations resulting from stimulus manipulations (of acoustic detail and predictiveness) as well as task-independent overall alpha power were related to subjective listening effort. The present data show that alpha dynamics is a promising neural marker of individual difficulties as well as age-related changes in sensation, perception, and comprehension in complex communication situations.

We present an extensive study of non-minimal flavour violation in the squark sector in the framework of the Minimal Supersymmetric Standard Model. We investigate the effects of multiple non-vanishing flavour-violating elements in the squark mass matrices by means of a Markov Chain Monte Carlo scanning technique and identify parameter combinations that are favoured by both current data and theoretical constraints. We then detail the resulting distributions of the flavour-conserving and flavour-violating model parameters. Based on this analysis, we propose a set of benchmark scenarios relevant for future studies of non-minimal flavour violation in the Minimal Supersymmetric Standard Model., 31 pages, 12 figures, 6 tables; SLHA files for non-minimally flavour-violating MSSM benchmark scenarios available as ancillary files; version to appear in JHEP

Chlamydophila psittaci was detected in 10% of 431 ful- mars examined from the Faroe Islands. Analysis of ompA showed a sequence almost identical to that of the type strain. The origin of C. psittaci outbreaks in fulmars is dis- cussed. Despite a high level of exposure, the risk for trans- mission of C. psittaci to humans is low.

Free-living wild birds worldwide act as reservoir for Chlamydia psittaci, but the risk of transmission to humans through contact with wild birds has not been widely documented. From 12 January to April 9 2013, a total of 25 cases of psittacosis were detected in southern Sweden, about a threefold increase compared with the mean of the previous 10 years. A matched case-control study investigating both domestic and wild bird exposure showed that cases were more likely than controls to have cleaned wild bird feeders or been exposed to wild bird droppings in other ways (OR: 10.1; 95% CI: 2.1-47.9). We recommend precautionary measures such as wetting bird feeders before cleaning them, to reduce the risk of transmission of C. psittaci when in contact with bird droppings. Furthermore, C. psittaci should be considered for inclusion in laboratory diagnostic routines when analysing samples from patients with atypical pneumonia, since our findings suggest that psittacosis is underdiagnosed.

Patients with the monogenic disease autoimmune polyendocrine syndrome type I (APS I) develop autoimmunity against multiple endocrine organs and suffer from chronic mucocutaneous candidiasis (CMC), a paradoxical complication with an unknown mechanism. We report that saliva from APS I patients with CMC was defective in inhibiting growth of C. albicans in vitro and had reduced levels of a salivary protein identified as cystatin SA1. In contrast, APS I patients with no CMC expressed salivary cystatin SA1 and could inhibit C. albicans to the same extent as healthy controls. We evaluated the anti-fungal activity of cystatin SA1 and found that synthesized full length cystatin SA1 efficiently inhibited growth of C. albicans in vitro. Moreover, APS I patients exhibited salivary IgA autoantibodies recognizing myosin-9, a protein expressed in the salivary glands that also produce cystatin SA1, thus linking autoimmunity to cystatin SA1 deficiency and CMC. This data suggests an autoimmune mechanism behind CMC in APS I and provide rationale for evaluating cystatin SA1 in antifungal therapy.

Despite the lack of experimental evidence, Supersymmetry remains an attractive candidate for physics beyond the standard model of particle physics. Simple and viable supersymmetric extensions, such as the Minimal Supersymmetric Standard Model, cure, among other shortcomings of the standard model, the electroweak hierarchy problem, the gauge coupling unification and provide attractive dark matter candidates.One of the general characteristics of such extensions is that they may present a non-trivial flavour structure, which can lead to sizable contributions to flavour violating processes which are precisely measured and can be used to constrain the parameter space of new physics. The purpose of this manuscript is to discuss aspects of the extended flavour structure within supersymmetric models.The manuscript will first introduce the Standard Model of particle physics and its supersymmetric extensions before exposing three research projects.The first one will treat the problematic of the reconstruction of the squark flavour structure. Here, we have employed different strategies relying on inference statistical methods together with machine learning algorithms and assuming that a squark-like state is to be observed at colliders. Being a first step in this direction, improvement and complementary study will need to be proposed in case of the actual observation of a squark-like state but the obtained results are appealing.As a second step, we shall discuss constraints and experimental signatures of SU(5) Grand Unified Theories including flavour symmetries. In this framework, we will focus on A4 family symmetry inspired models. This analysis is based on a numerical scan of the parameter space, including experimental flavour constraints as well as dark matter relic density. The results show, as it has already been pointed out before, that the lepton sector is much more constraining that the hadronic one. Additionally, interesting features arise in case of a simultaneous scan over the flavour violating parameters, and suggest that the allowed ranges for these parameters are larger than in the case of a single parameter study because of correlation effects.Finally, the last chapter will be dedicated to leptoquark extensions of the standard model. These models, not necessary supersymmetric, have received considerable attention over the past few years, mainly due to the potential observation of lepton non universality at the Large Hadron Collider. We will discuss such extensions in the context of discrete flavour symmetries, useful tool for constraining the leptoquark patterns to a very predictive form. Finally, a model independent scan will be exposed, where we have obtained a list of potential symmetry candidates able to reproduce very specific leptoquark patterns alongside to the standard model fermionic mixing; Malgré l'absence de signatures expérimentales, les extensions supersymétriques du modèle standard de la physique des particules sont encore considérées parmi les plus attractives. La supersymétrie permet entre autres de résoudre le problème de la hiérarchie électrofaible, favorise l'unification des couplages de jauge nécessaire à une construction réaliste d'une théorie de grande unification, et propose des candidats viable à la matière noire.Une des caractéristiques générale des extensions supersymétriques est de présenter une structure de saveur nouvelle, pouvant entraîner de larges contributions dans les observables de violation de la saveur. L'étude de certaines de ces structures et de leurs conséquences expérimentales est l'objet de ce manuscrit.Ce manuscrit débutera avec une introduction générale au modèle standard de la physique des particules et de ses extensions supersymétriques avant de présenter trois projets de recherche.Dans le premier travail exposé, nous aborderons des approches permettant d'identifier la structure de saveur dans le secteur des squarks (partenaire supersymétrique des quarks). Ces méthodes, pionnières pour la problématique, reposent sur l'observation hypothétique d'un squark et utilisent des méthodes d'inférence statistique et de "machine learning". Bien qu'il ne s'agisse que d'une première approche, les résultats sont encourageants et la méthode pourrait être développée en cas d'observation réelle d'un état semblable à un squark aux collisionneurs.Nous discuterons ensuite de contraintes et conséquences expérimentales présentes dans des modèles de grande unification du type SU(5) avec symétrie de saveur. Dans ce contexte, nous discuterons de modèles inspirés par le groupe A_4. Cette analyse propose une exploration de l'espace des paramètres de ce type de modèles en incluant les contraintes expérimentales de saveur ainsi que la densité relique de matière noire. Les résultats confirment que le secteur leptonique est bien plus contraignant que le secteur hadronique. En addition, plusieurs particularités émergent lors d'une exploration simultanée de l'ensemble des paramètres conduisant à un espace autorisé par les contraintes plus important que dans le cas d'étude ne variant qu'un paramètre à la fois.Finalement, le dernier chapitre de ce manuscrit sera dédié à la discussion d'extensions du modèle standard incluant des leptoquarks. Ces extensions, non nécessairement supersymétriques, ont reçu un regain d'attention ces dernières années, en particulier suite à des mesures qui suggéreraient l'existence de structure non universelle de saveur leptonique. Nous discuterons de ces extensions dans le contexte des symétries discrètes de saveur qui peuvent conduire à des structures de couplages très prédictifs. Enfin, une méthode indépendante de modèles sera proposée pour obtenir une liste de groupes candidats à la reproduction de ces structures de couplages et de mélange fermionique du modèle standard de façon simultanée.

The Minimal Supersymmetric Standard Model (MSSM) is probably the best studied of all new physics theories. In most phenomenological studies, one assumes the hypothesis of minimal flavour violation, where all flavour-violating interactions are related to the CKM-matrix (as it is the case in the standard model). However, if supersymmetry is embedded in larger frameworks such as grand unified theories (GUT), new sources of flavour violation can appear. The corresponding terms in the Lagrangian are directly related to the mechanism of supersymmetry breaking, for which at present no theoretical consensus exists. Several processes have recently been evoked (among others by the co-director of the proposed thesis), which might lead to promising signatures at the LHC if non-minimal flavour violation is realized. These studies, however, included flavour-violating terms directly at the electroweak scale without taking into account their possible origin at some high scale. The main goal of the project is to extend the previous work in order to take into account the link between the electroweak and the GUT scale. This will allow to put constraints on parameters describing supersymmetry breaking using constraints imposed at the electroweak scale. A second goal is the analysis of relevant processes with the help of current Monte-Carlo simulation tools in order to study the background and thus clarify the observability at LHC for different scenarios and regions of parameters space. So, the project is ideally situated at the frontier between model building and more phenomenological aspects. For this reason the project naturally includes interactions with the local particle physics phenomenology group at LAPTh as well as with the the neighbouring experimental groups (e.g. ATLAS, LHCb) at LAPP. Moreover, collaborations on the national, in particular with the LPSC Grenoble, and international level, e.g. with the University of Würzburg (Germany), the University of Münster (Germany) and the newly created International Institute of Physics in Natal (Brasil) are envisaged.; Le modèle standard supersymétrique minimal (MSSM) est probablement une des théories de nouvelle physique les plus étudiées. Dans la plupart des études phénoménologiques, on fait l'hypothèse de la violation minimale de la saveur dans laquelle toutes les interactions violant la saveur sont directement liées à la matrice CKM du modèle Standard. Cependant, si la supersymétrie est plongée dans des cadres plus larges tels que les théories dites de Grande Unification, de nouvelles sources de violation de la saveur peuvent apparaitre. Les termes correspondant dans le lagrangien sont directement liés au choix du mécanisme de brisure de la supersymétrie. Or, à l'heure actuelle, aucun consensus n’existe quant au choix exact du mécanisme de brisure de la SUSY. Plusieurs mécanismes ont été évoqués récemment (entre autre, par le co-directeur de la thèse), qui pourraient conduire à des signatures prometteuses au LHC pour différents scénarios et domaines de paramètre. Le projet est donc idéalement situé à la frontière entre le 'model building' et des aspects plus phénoménologiques. Pour cette raison, le thésard sera naturellement amené à interagir de manière active avec le groupe de phénoménologie de physique des particules du LAPTh ainsi qu'avec les groupes de physique des particules du LAPP (ATLAS, LHCb..), laboratoire expérimental partageant le même bâtiment que le LAPTh. De plus, des collaborations sur le plan national, en particulier avec le LPSC de Grenoble, ainsi que sur le plan international, avec les universités de Würzburg et Münster (Allemagne) et le nouvel institut de physique de NATAL (Brésil) sont également envisagées.