Genetics of Chronic Lymphocytic Leukemia: Practical Aspects and Prognostic Significance

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Endometrial osteoid metaplasia.

editorial reviewedEndometrial osteoid metaplasia is a rare condition characterised by the presence of bone in the uterine cavity. The main symptoms are secondary infertility, cycle disorders or dysmenorrhea. The discovery can also be fortuitous. Ultrasound and diagnostic hysteroscopy are diagnostic tools while operative hysteroscopy provides treatment. In the vast majority of cases, it is discovered in the aftermath of pregnancy, especially after curettage or miscarriage. There are several theories as to its etiopathogenesis.La métaplasie ostéoïde est définie par la présence de tissu osseux au niveau de l’endomètre. Il s’agit d’une affection rare. Les principaux symptômes sont l’infertilité secondaire, des troubles du cycle ou de la dysménorrhée. La découverte peut également être fortuite. L’échographie et l’hystéroscopie diagnostique sont des outils de diagnostic tandis que l’hystéroscopie opératoire assure le traitement. Dans la grande majorité des cas, elle est découverte dans les suites d’une grossesse, surtout après un curetage ou une fausse-couche. Il existe plusieurs théories quant à son étiopathogénie

Assessment of non-genetic parameters of the racing performances of Arabian and Thoroughbred horses in Algeria

From 1995 to 2007, flat racing data was collected for Thoroughbred and Arabian horses in Algeria. Non-genetic factors affecting racing performances have been identified and quantified using linear models. Performances are represented through the earnings and the rankings. Three traits were used: two earnings traits [the logarithm of annual virtual earnings (LAEV) and the logarithm of average annual virtual earnings per start (LAEV/S)], and one rank trait (the ranking transformed and normalised by application of the “performance rate” procedure, PERF). The results showed significant positive correlations (p < 0.001) between the three traits in the two breeds, showing that the measurements quantify similar - although different - aptitudes. The effects of sex, age, year of the performance and the interactions between age and sex and between age and year of the race turned out to be significant (p < 0.05) for the three traits LAEV, LAEV/S and PERF for the Arabian horses. However, for Thoroughbreds, the sex effect was only significant for the PERF trait and an interaction between the age and year of the performance was the only significant interaction (p < 0.001) for the LAEV trait. The effects of these non-genetic factors will be used to correct the raw measures in a future genetic evaluation.Key words: Earnings, non-genetic factors, flat racing, race-horses, rankings, Algeria

Study of flavour dependencies in leptogenesis

We study the impact of flavours on the efficiency factors and give analytical and numerical results of the baryon asymmetry taking into account the different charged lepton Yukawa contributions and the complete (diagonal and off-diagonal) $L$ to $B-L$ conversion $A$ matrix. With this treatment we update the lower bound on the lightest right-handed neutrino mass.Comment: 13 pages, 11 figures. typos corrected, some formulae modified. 2 figures and discussion adde

Vietnamese chickens: a gate towards Asian genetic diversity

BACKGROUND: Chickens represent an important animal genetic resource and the conservation of local breeds is an issue for the preservation of this resource. The genetic diversity of a breed is mainly evaluated through its nuclear diversity. However, nuclear genetic diversity does not provide the same information as mitochondrial genetic diversity. For the species Gallus gallus, at least 8 maternal lineages have been identified. While breeds distributed westward from the Indian subcontinent usually share haplotypes from 1 to 2 haplogroups, Southeast Asian breeds exhibit all the haplogroups. The Vietnamese Ha Giang (HG) chicken has been shown to exhibit a very high nuclear diversity but also important rates of admixture with wild relatives. Its geographical position, within one of the chicken domestication centres ranging from Thailand to the Chinese Yunnan province, increases the probability of observing a very high genetic diversity for maternal lineages, and in a way, improving our understanding of the chicken domestication process. RESULTS: A total of 106 sequences from Vietnamese HG chickens were first compared to the sequences of published Chinese breeds. The 25 haplotypes observed in the Vietnamese HG population belonged to six previously published haplogroups which are: A, B, C, D, F and G. On average, breeds from the Chinese Yunnan province carried haplotypes from 4.3 haplogroups. For the HG population, haplogroup diversity is found at both the province and the village level (0.69).The AMOVA results show that genetic diversity occurred within the breeds rather than between breeds or provinces. Regarding the global structure of the mtDNA diversity per population, a characteristic of the HG population was the occurrence of similar pattern distribution as compared to G. gallus spadiceus. However, there was no geographical evidence of gene flow between wild and domestic populations as observed when microsatellites were used. CONCLUSIONS: In contrast to other chicken populations, the HG chicken population showed very high genetic diversity at both the nuclear and mitochondrial levels. Due to its past and recent history, this population accumulates a specific and rich gene pool highlighting its interest and the need for conservation

Immunopeptidomics of colorectal cancer organoids reveals a sparse HLA class I neoantigen landscape and no increase in neoantigens with interferon or MEK-inhibitor treatment.

Patient derived organoids (PDOs) can be established from colorectal cancers (CRCs) as in vitro models to interrogate cancer biology and its clinical relevance. We applied mass spectrometry (MS) immunopeptidomics to investigate neoantigen presentation and whether this can be augmented through interferon gamma (IFNγ) or MEK-inhibitor treatment. Four microsatellite stable PDOs from chemotherapy refractory and one from a treatment naïve CRC were expanded to replicates with 100 million cells each, and HLA class I and class II peptide ligands were analyzed by MS. We identified an average of 9936 unique peptides per PDO which compares favorably against published immunopeptidomics studies, suggesting high sensitivity. Loss of heterozygosity of the HLA locus was associated with low peptide diversity in one PDO. Peptides from genes without detectable expression by RNA-sequencing were rarely identified by MS. Only 3 out of 612 non-silent mutations encoded for neoantigens that were detected by MS. In contrast, computational HLA binding prediction estimated that 304 mutations could generate neoantigens. One hundred ninety-six of these were located in expressed genes, still exceeding the number of MS-detected neoantigens 65-fold. Treatment of four PDOs with IFNγ upregulated HLA class I expression and qualitatively changed the immunopeptidome, with increased presentation of IFNγ-inducible genes. HLA class II presented peptides increased dramatically with IFNγ treatment. MEK-inhibitor treatment showed no consistent effect on HLA class I or II expression or the peptidome. Importantly, no additional HLA class I or II presented neoantigens became detectable with any treatment. Only 3 out of 612 non-silent mutations encoded for neoantigens that were detectable by MS. Although MS has sensitivity limits and biases, and likely underestimated the true neoantigen burden, this established a lower bound of the percentage of non-silent mutations that encode for presented neoantigens, which may be as low as 0.5%. This could be a reason for the poor responses of non-hypermutated CRCs to immune checkpoint inhibitors. MEK-inhibitors recently failed to improve checkpoint-inhibitor efficacy in CRC and the observed lack of HLA upregulation or improved peptide presentation may explain this

The see-saw mechanism: neutrino mixing, leptogenesis and lepton flavor violation

The see-saw mechanism to generate small neutrino masses is reviewed. After summarizing our current knowledge about the low energy neutrino mass matrix we consider reconstructing the see-saw mechanism. Low energy neutrino physics is not sufficient to reconstruct see-saw, a feature which we refer to as ``see-saw degeneracy''. Indirect tests of see-saw are leptogenesis and lepton flavor violation in supersymmetric scenarios, which together with neutrino mass and mixing define the framework of see-saw phenomenology. Several examples are given, both phenomenological and GUT-related. Variants of the see-saw mechanism like the type II or triplet see-saw are also discussed. In particular, we compare many general aspects regarding the dependence of LFV on low energy neutrino parameters in the extreme cases of a dominating conventional see-saw term or a dominating triplet term. For instance, the absence of mu -> e gamma or tau -> e gamma in the pure triplet case means that CP is conserved in neutrino oscillations. Scanning models, we also find that among the decays mu -> e gamma, tau -> e gamma and tau -> mu gamma the latter one has the largest branching ratio in (i) SO(10) type I see-saw models and in (ii) scenarios in which the triplet term dominates in the neutrino mass matrix.Comment: 26 pages, 7 figures. Expanded version of talk given at 10th Workshop In High Energy Physics Phenomenology (WHEPP 10), January 2008, Chennai, India. Typos corrected, comments and references adde

Towards constraints on the SUSY seesaw from flavour-dependent leptogenesis

We systematically investigate constraints on the parameters of the supersymmetric type-I seesaw mechanism from the requirement of successful thermal leptogenesis in the presence of upper bounds on the reheat temperature $T_\mathrm{RH}$ of the early Universe. To this end, we solve the flavour-dependent Boltzmann equations in the MSSM, extended to include reheating. With conservative bounds on $T_\mathrm{RH}$, leading to mildly constrained scenarios for thermal leptogenesis, compatibility with observation can be obtained for extensive new regions of the parameter space, due to flavour-dependent effects. On the other hand, focusing on (normal) hierarchical light and heavy neutrinos, the hypothesis that there is no CP violation associated with the right-handed neutrino sector, and that leptogenesis exclusively arises from the CP-violating phases of the $U_\text{MNS}$ matrix, is only marginally consistent. Taking into account stricter bounds on $T_\mathrm{RH}$ further suggests that (additional) sources of CP violation must arise from the right-handed neutrino sector, further implying stronger constraints for the right-handed neutrino parameters.Comment: 42 pages, 12 figures; final version published in JCAP; numerical results for the efficiency factor can be downloaded from http://www.newphysics.eu/leptogenesis