Gene conversion in human rearranged immunoglobulin genes

Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V<sub>H</sub> segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V<sub>H</sub> replacements with no addition of untemplated nucleotides at the V<sub>H</sub>–V<sub>H</sub> joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V<sub>H</sub> replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion

Viral discovery and diversity in trypanosomatid protozoa with a focus on relatives of the human parasite <i>Leishmania</i>.

Knowledge of viral diversity is expanding greatly, but many lineages remain underexplored. We surveyed RNA viruses in 52 cultured monoxenous relatives of the human parasite &lt;i&gt;Leishmania&lt;/i&gt; ( &lt;i&gt;Crithidia&lt;/i&gt; and &lt;i&gt;Leptomonas&lt;/i&gt; ), as well as plant-infecting &lt;i&gt;Phytomonas&lt;/i&gt; &lt;i&gt;Leptomonas pyrrhocoris&lt;/i&gt; was a hotbed for viral discovery, carrying a virus (Leptomonas pyrrhocoris ostravirus 1) with a highly divergent RNA-dependent RNA polymerase missed by conventional BLAST searches, an emergent clade of tombus-like viruses, and an example of viral endogenization. A deep-branching clade of trypanosomatid narnaviruses was found, notable as &lt;i&gt;Leptomonas seymouri&lt;/i&gt; bearing Narna-like virus 1 (LepseyNLV1) have been reported in cultures recovered from patients with visceral leishmaniasis. A deep-branching trypanosomatid viral lineage showing strong affinities to bunyaviruses was termed " &lt;i&gt;Leishbunyavirus&lt;/i&gt; " (LBV) and judged sufficiently distinct to warrant assignment within a proposed family termed " &lt;i&gt;Leishbunyaviridae&lt;/i&gt; " Numerous relatives of trypanosomatid viruses were found in insect metatranscriptomic surveys, which likely arise from trypanosomatid microbiota. Despite extensive sampling we found no relatives of the totivirus &lt;i&gt;Leishmaniavirus&lt;/i&gt; (LRV1/2), implying that it was acquired at about the same time the &lt;i&gt;Leishmania&lt;/i&gt; became able to parasitize vertebrates. As viruses were found in over a quarter of isolates tested, many more are likely to be found in the &gt;600 unsurveyed trypanosomatid species. Viral loss was occasionally observed in culture, providing potentially isogenic virus-free lines enabling studies probing the biological role of trypanosomatid viruses. These data shed important insights on the emergence of viruses within an important trypanosomatid clade relevant to human disease

Small ball probability, Inverse theorems, and applications

Let $\xi$ be a real random variable with mean zero and variance one and $A={a_1,...,a_n}$ be a multi-set in $\R^d$. The random sum $$S_A := a_1 \xi_1 + ... + a_n \xi_n$$ where $\xi_i$ are iid copies of $\xi$ is of fundamental importance in probability and its applications. We discuss the small ball problem, the aim of which is to estimate the maximum probability that $S_A$ belongs to a ball with given small radius, following the discovery made by Littlewood-Offord and Erdos almost 70 years ago. We will mainly focus on recent developments that characterize the structure of those sets $A$ where the small ball probability is relatively large. Applications of these results include full solutions or significant progresses of many open problems in different areas.Comment: 47 page

Ultrahigh-energy neutrino follow-up of Gravitational Wave events GW150914 and GW151226 with the Pierre Auger Observatory

On September 14, 2015 the Advanced LIGO detectors observed their first gravitational-wave (GW) transient GW150914. This was followed by a second GW event observed on December 26, 2015. Both events were inferred to have arisen from the merger of black holes in binary systems. Such a system may emit neutrinos if there are magnetic fields and disk debris remaining from the formation of the two black holes. With the surface detector array of the Pierre Auger Observatory we can search for neutrinos with energy above 100 PeV from point-like sources across the sky with equatorial declination from about -65 deg. to +60 deg., and in particular from a fraction of the 90% confidence-level (CL) inferred positions in the sky of GW150914 and GW151226. A targeted search for highly-inclined extensive air showers, produced either by interactions of downward-going neutrinos of all flavors in the atmosphere or by the decays of tau leptons originating from tau-neutrino interactions in the Earth's crust (Earth-skimming neutrinos), yielded no candidates in the Auger data collected within $\pm 500$ s around or 1 day after the coordinated universal time (UTC) of GW150914 and GW151226, as well as in the same search periods relative to the UTC time of the GW candidate event LVT151012. From the non-observation we constrain the amount of energy radiated in ultrahigh-energy neutrinos from such remarkable events.Comment: Published version. Added journal reference and DOI. Added Report Numbe

Multi-resolution anisotropy studies of ultrahigh-energy cosmic rays detected at the Pierre Auger Observatory

We report a multi-resolution search for anisotropies in the arrival directions of cosmic rays detected at the Pierre Auger Observatory with local zenith angles up to $80^\circ$ and energies in excess of 4 EeV ($4 \times 10^{18}$ eV). This search is conducted by measuring the angular power spectrum and performing a needlet wavelet analysis in two independent energy ranges. Both analyses are complementary since the angular power spectrum achieves a better performance in identifying large-scale patterns while the needlet wavelet analysis, considering the parameters used in this work, presents a higher efficiency in detecting smaller-scale anisotropies, potentially providing directional information on any observed anisotropies. No deviation from isotropy is observed on any angular scale in the energy range between 4 and 8 EeV. Above 8 EeV, an indication for a dipole moment is captured; while no other deviation from isotropy is observed for moments beyond the dipole one. The corresponding $p$-values obtained after accounting for searches blindly performed at several angular scales, are $1.3 \times 10^{-5}$ in the case of the angular power spectrum, and $2.5 \times 10^{-3}$ in the case of the needlet analysis. While these results are consistent with previous reports making use of the same data set, they provide extensions of the previous works through the thorough scans of the angular scales.Comment: Published version. Added journal reference and DOI. Added Report Numbe

Male fertility: summary overview of the publications January – March 2022

The article presents an overview of the most significant publications on the topic of male infertility. The main selection criteria were the practical significance of the article, as well as the impact factor of the journal in which it was published, according to the SCImago Journal Rank (SJR). As a result, a list of 10 papers published in the first quarter (January – March) of 2022 was compiled. The review includes articles on the following issues: the role of coronavirus infection in male infertility, the effectiveness of aromatase inhibitors in infertile men, the effect of assisted reproductive technologies on the reproductive health of descendants, recurrent miscarriage, the effect of antibiotic therapy on the DNA fragmentation index, the role of antisperm antibodies in male infertility, the incidence of idiopathic male infertility, the Sixth Edition WHO guidelines for the ejaculate processing, as well as the relationship of depression with male infertility

Calibration of the Logarithmic-Periodic Dipole Antenna (LPDA) Radio Stations at the Pierre Auger Observatory using an Octocopter

An in-situ calibration of a logarithmic periodic dipole antenna with a frequency coverage of 30 MHz to 80 MHz is performed. Such antennas are part of a radio station system used for detection of cosmic ray induced air showers at the Engineering Radio Array of the Pierre Auger Observatory, the so-called Auger Engineering Radio Array (AERA). The directional and frequency characteristics of the broadband antenna are investigated using a remotely piloted aircraft (RPA) carrying a small transmitting antenna. The antenna sensitivity is described by the vector effective length relating the measured voltage with the electric-field components perpendicular to the incoming signal direction. The horizontal and meridional components are determined with an overall uncertainty of 7.4^{+0.9}_{-0.3} % and 10.3^{+2.8}_{-1.7} % respectively. The measurement is used to correct a simulated response of the frequency and directional response of the antenna. In addition, the influence of the ground conductivity and permittivity on the antenna response is simulated. Both have a negligible influence given the ground conditions measured at the detector site. The overall uncertainties of the vector effective length components result in an uncertainty of 8.8^{+2.1}_{-1.3} % in the square root of the energy fluence for incoming signal directions with zenith angles smaller than 60{\deg}.Comment: Published version. Updated online abstract only. Manuscript is unchanged with respect to v2. 39 pages, 15 figures, 2 table

Male fertility: a summary overview of the publications April – September 2022

The article provides an overview of the most significant publications on male infertility. The main selection criteria were the practical relevance of the article, as well as the impact factor of the journal it was published, according to the SCImago Journal Rank (SJR). As a result, a list of 10 papers published in Q2-Q3 (April — September) 2022 was formed. The summary overview includes articles on the following topics: role of coronavirus infection in disorders of spermatogenesis, efficacy of hormonal stimulation before surgical sperm extraction, therapy consequences of diabetes mellitus on progeny reproductive health, new methods for selecting spermatozoa in ICSI, the efficacy of antioxidants, the safety of vaccines against SARS-CoV-2, the importance of genetic tests and predictive factors for micro-TESE success

Male fertility: a review of the publications July — September 2021

The article provides an overview of the most significant publications on the topic of male infertility. The main selection criteria were considered the practical significance of the article, as well as the impact factor of the journal in which it was published according to the SCImago Journal Rank (SJR). As a result, we formed a list of 10 articles published in the III quarter (July — September) of 2021. The review included articles concerning the following issues: the ability of oocytes to repair damaged DNA-chains of sperm cells, the effectiveness of ICSI in AZF-c microdeletions, the advanced paternal age, artificial intelligence in reproductive clinics, genetic causes of infertility, the effect of surgical treatment of varicocele concerning DNA fragmentation, the role of ICSI in the frequency of chromosomal abnormalities in offspring, the safety of COVID-19 vaccination for spermatogenesis, as well as the novel WHO 6 manual for semen investigation

Elite opinion and foreign policy in post-communist Russia

Russian elite opinion on matters of foreign policy may be classified as ‘Liberal Westerniser’, ‘Pragmatic Nationalist’ and ‘Fundamentalist Nationalist’, terms that reflect longstanding debates about the country’s relationship with the outside world. An analysis of press statements and election manifestoes together with a programme of elite interviews between 2004 and 2006 suggests a clustering of opinion on a series of strategic issues. Liberal Westernisers seek the closest possible relationship with Europe, and favour eventual membership of the EU and NATO. Pragmatic Nationalists are more inclined to favour practical co-operation, and do not assume an identity of values or interests with the Western countries. Fundamentalist Nationalists place more emphasis on the other former Soviet republics, and on Asia as much as Europe, and see the West as a threat to Russian values as well as to its state interests. Each of these positions, in turn, draws on an identifiable set of domestic constituencies: Liberal Westernisers on the promarket political parties, Pragmatic Nationalists on the presidential administration and defence and security ministries, and Fundamentalist Nationalists on the Orthodox Church and Communists