Persisting Viral Sequences Shape Microbial CRISPR-based Immunity

Well-studied innate immune systems exist throughout bacteria and archaea, but a more recently discovered genomic locus may offer prokaryotes surprising immunological adaptability. Mediated by a cassette-like genomic locus termed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), the microbial adaptive immune system differs from its eukaryotic immune analogues by incorporating new immunities unidirectionally. CRISPR thus stores genomically recoverable timelines of virus-host coevolution in natural organisms refractory to laboratory cultivation. Here we combined a population genetic mathematical model of CRISPR-virus coevolution with six years of metagenomic sequencing to link the recoverable genomic dynamics of CRISPR loci to the unknown population dynamics of virus and host in natural communities. Metagenomic reconstructions in an acid-mine drainage system document CRISPR loci conserving ancestral immune elements to the base-pair across thousands of microbial generations. This ‘trailer-end conservation’ occurs despite rapid viral mutation and despite rapid prokaryotic genomic deletion. The trailer-ends of many reconstructed CRISPR loci are also largely identical across a population. ‘Trailer-end clonality’ occurs despite predictions of host immunological diversity due to negative frequency dependent selection (kill the winner dynamics). Statistical clustering and model simulations explain this lack of diversity by capturing rapid selective sweeps by highly immune CRISPR lineages. Potentially explaining ‘trailer-end conservation,’ we record the first example of a viral bloom overwhelming a CRISPR system. The polyclonal viruses bloom even though they share sequences previously targeted by host CRISPR loci. Simulations show how increasing random genomic deletions in CRISPR loci purges immunological controls on long-lived viral sequences, allowing polyclonal viruses to bloom and depressing host fitness. Our results thus link documented patterns of genomic conservation in CRISPR loci to an evolutionary advantage against persistent viruses. By maintaining old immunities, selection may be tuning CRISPR-mediated immunity against viruses reemerging from lysogeny or migration

Measurement of the pn→ppπ0π−pn \to pp\pi^0\pi^- Reaction in Search for the Recently Observed Resonance Structure in dπ0π0d\pi^0\pi^0 and dπ+π−d\pi^+\pi^- systems

Exclusive measurements of the quasi-free $pn \to pp\pi^0\pi^-$ reaction have been performed by means of $pd$ collisions at $T_p$ = 1.2 GeV using the WASA detector setup at COSY. Total and differential cross sections have been obtained covering the energy region $\sqrt s$ = (2.35 - 2.46) GeV, which includes the region of the ABC effect and its associated resonance structure. No ABC effect, {\it i.e.} low-mass enhancement is found in the $\pi^0\pi^-$-invariant mass spectrum -- in agreement with the constraint from Bose statistics that the isovector pion pair can not be in relative s-wave. At the upper end of the covered energy region $t$-channel processes for Roper, $\Delta(1600)$ and $\Delta\Delta$ excitations provide a reasonable description of the data, but at low energies the measured cross sections are much larger than predicted by such processes. Adding a resonance amplitude for the resonance at $m$=~2.37 GeV with $\Gamma$ =~70 MeV and $I(J^P)=~0(3^+)$ observed recently in $pn \to d\pi^0\pi^0$ and $pn \to d\pi^+\pi^-$ reactions leads to an agreement with the data also at low energies

Search for a dark photon in the π0→e+e−γ\pi^0 \to e^+e^-\gamma decay

The presently world largest data sample of pi0 --> gamma e+e- decays containing nearly 5E5 events was collected using the WASA detector at COSY. A search for a dark photon U produced in the pi0 --> gamma U --> gamma e+e- decay from the pp-->pp\pi^0 reaction was carried out. An upper limit on the square of the U-gamma mixing strength parameter epsilon^2 of 5e-6 at 90% CL was obtained for the mass range 20 MeV <M_U< 100 MeV. This result together with other recent experimental limits significantly reduces the M_U vs. \epsilon^2 parameter space preferred by the measured value of the muon anomalous magnetic moment.Comment: 16 pages, 8 figures; improved analysis extending the exclusion region to 20 MeV<M_U< 100 MeV; implemented changes requested by referee

Subarachnoid Space: New Tricks by an Old Dog

PURPOSE: The purpose of the study was to: (1) evaluate the subarachnoid space (SAS) width and pial artery pulsation in both hemispheres, and (2) directly compare magnetic resonance imaging (MRI) to near-infrared transillumination/backscattering sounding (NIR-T/BSS) measurements of SAS width changes in healthy volunteers. METHODS: The study was performed on three separate groups of volunteers, consisting in total of 62 subjects (33 women and 29 men) aged from 16 to 39 years. SAS width was assessed by MRI and NIR-T/BSS, and pial artery pulsation by NIR-T/BSS. RESULTS: In NIR-T/BSS, the right frontal SAS was 9.1% wider than the left (p<0.01). The SAS was wider in men (p<0.01), while the pial artery pulsation was higher in women (p<0.01). Correlation and regression analysis of SAS width changes between the back- and abdominal-lying positions measured with MRI and NIRT-B/SS demonstrated high interdependence between both methods (r = 0.81, p<0.001). CONCLUSIONS: NIR-T/BSS and MRI were comparable and gave equivalent modalities for the SAS width change measurements. The SAS width and pial artery pulsation results obtained with NIR-T/BSS are consistent with the MRI data in the literature related to sexual dimorphism and morphological asymmetries between the hemispheres. NIR-T/BSS is a potentially cheap and easy-to-use method for early screening in patients with brain tumours, increased intracranial pressures and other abnormalities. Further studies in patients with intracranial pathologies are warranted

\pi^0 \pi^0 Production in Proton-Proton Collisions at Tp=1.4 GeV

The reaction pp->pppi0pi0 has been investigated at a beam energy of 1.4 GeV using the WASA-at-COSY facility. The total cross section is found to be (324 +- 21_systematic +- 58_normalization) mub. In order to to study the production mechanism, differential kinematical distributions have been evaluated. The differential distributions indicate that both initial state protons are excited into intermediate Delta(1232) resonances, each decaying into a proton and a single pion, thereby producing the pion pair in the final state. No significant contribution of the Roper resonance N*(1440) via its decay into a proton and two pions is foundComment: Submitted to PL

Universal Artifacts Affect the Branching of Phylogenetic Trees, Not Universal Scaling Laws

The superficial resemblance of phylogenetic trees to other branching structures allows searching for macroevolutionary patterns. However, such trees are just statistical inferences of particular historical events. Recent meta-analyses report finding regularities in the branching pattern of phylogenetic trees. But is this supported by evidence, or are such regularities just methodological artifacts? If so, is there any signal in a phylogeny?In order to evaluate the impact of polytomies and imbalance on tree shape, the distribution of all binary and polytomic trees of up to 7 taxa was assessed in tree-shape space. The relationship between the proportion of outgroups and the amount of imbalance introduced with them was assessed applying four different tree-building methods to 100 combinations from a set of 10 ingroup and 9 outgroup species, and performing covariance analyses. The relevance of this analysis was explored taking 61 published phylogenies, based on nucleic acid sequences and involving various taxa, taxonomic levels, and tree-building methods.All methods of phylogenetic inference are quite sensitive to the artifacts introduced by outgroups. However, published phylogenies appear to be subject to a rather effective, albeit rather intuitive control against such artifacts. The data and methods used to build phylogenetic trees are varied, so any meta-analysis is subject to pitfalls due to their uneven intrinsic merits, which translate into artifacts in tree shape. The binary branching pattern is an imposition of methods, and seldom reflects true relationships in intraspecific analyses, yielding artifactual polytomies in short trees. Above the species level, the departure of real trees from simplistic random models is caused at least by two natural factors--uneven speciation and extinction rates; and artifacts such as choice of taxa included in the analysis, and imbalance introduced by outgroups and basal paraphyletic taxa. This artifactual imbalance accounts for tree shape convergence of large trees.There is no evidence for any universal scaling in the tree of life. Instead, there is a need for improved methods of tree analysis that can be used to discriminate the noise due to outgroups from the phylogenetic signal within the taxon of interest, and to evaluate realistic models of evolution, correcting the retrospective perspective and explicitly recognizing extinction as a driving force. Artifacts are pervasive, and can only be overcome through understanding the structure and biological meaning of phylogenetic trees. Catalan Abstract in Translation S1

Domestic dog health worsens with socio-economic deprivation of their home communities

Dogs play an important role in infectious disease transmission as reservoir hosts of many zoonotic and wildlife pathogens. Nevertheless, unlike wildlife species involved in the life cycle of pathogens, whose health status might be a direct reflection of their fitness and competitive abilities, dog health condition could be sensitive to socio-economic factors impacting the well-being of their owners. Here, we compare several dog health indicators in three rural communities of Panama with different degrees of socio-economic deprivation. From a total of 78 individuals, we collected blood and fecal samples, and assessed their body condition. With the blood samples, we performed routine hematologic evaluation (complete blood counts) and measured cytokine levels (Interferon-γ and Interleukin-10) through enzyme-linked immunosorbent assays. With the fecal samples we diagnosed helminthiases. Dogs were also serologically tested for exposure to Trypanosoma cruzi and canine distemper virus, and molecular tests were done to assess T. cruzi infection status. We found significant differences between dog health measurements, pathogen prevalence, parasite richness, and economic status of the human communities where the dogs lived. We found dogs that were less healthy, more likely to be infected with zoonotic pathogens, and more likely to be seropositive to canine distemper virus in the communities with lower economic status. This study concludes that isolated communities of lower economic status in Panama may have less healthy dogs that could become major reservoirs in the transmission of diseases to humans and sympatric wildlife

Isospin decomposition of the basic double-pionic fusion in the region of the ABC effect WASA-at-COSY Collaboration

Exclusive and kinematically complete high-statistics measurements of the basic double-pionic fusion reactions pn → dπ 0 π 0 , pn → dπ + π − and pp → dπ + π 0 have been carried out simultaneously over the energy region of the ABC effect using the WASA detector setup at COSY. Whereas the isoscalar reaction part given by the dπ 0 π 0 channel exhibits the ABC effect, i.e. a low-mass enhancement in the ππ-invariant mass distribution, as well as the associated resonance structure in the total cross section, the isovector part given by the dπ + π 0 channel shows a smooth behavior consistent with the conventional tchannel process. The dπ + π − data are very well reproduced by combining the data for isovector and isoscalar contributions, if the kinematical consequences of the isospin violation due to different masses for charged and neutral pions are taken into account

Alexander Baumgarten on the Principle of Sufficicent Reason

This paper defends the Principle of Sufficient Reason, taking Baumgarten as its guide. The primary aim is not to vindicate the principle, but rather to explore the kinds of resources Baumgarten originally thought sufficient to justify the PSR against its early opponents. The paper also considers Baumgarten’s possible responses to Kant’s pre-Critical objections to the proof of the PSR. The paper finds that Baumgarten possesses reasonable responses to all these objections. While the paper notes that in the absence of a response to Kant’s Critical discussion of the PSR (which is omitted here due to limitations of space), this result does not vindicate the principle, it shows how this discussion provides a deeper understanding of what, according to Baumgarten, the PSR really assumes and intends, and prepares the way for a more responsible discussion of Kant’s critical objections to Baumgarten’s supposed proof.info:eu-repo/semantics/publishedVersio

High resolution optical refractometer for dispersion measurement in UV-NIR range

A high resolution optical refractometer for dispersion measurement in the UV-NIR range is described. Using this refractometer, refractive index of a range of liquid samples, such as aqueous solutions of sugars, salts and alcohols, was measured as a function of wavelength in the range from 300 nm to 920 nm with accuracy better than 10 - 5. So accurate results can be used for improvement of resolution of OCT measurements conducted in biological samples