Proteomes of Lactobacillus delbrueckii subsp. bulgaricus LBB.B5 Incubated in Milk at Optimal and Low Temperatures.

We identified the proteins synthesized by Lactobacillus delbrueckii subsp. bulgaricus strain LBB.B5 in laboratory culture medium (MRS) at 37°C and milk at 37 and 4°C. Cell-associated proteins were measured by gel-free, shotgun proteomics using high-performance liquid chromatography coupled with tandem mass spectrophotometry. A total of 635 proteins were recovered from all cultures, among which 72 proteins were milk associated (unique or significantly more abundant in milk). LBB.B5 responded to milk by increasing the production of proteins required for purine biosynthesis, carbohydrate metabolism (LacZ and ManM), energy metabolism (TpiA, PgK, Eno, SdhA, and GapN), amino acid synthesis (MetE, CysK, LBU0412, and AspC) and transport (GlnM and GlnP), and stress response (Trx, MsrA, MecA, and SmpB). The requirement for purines was confirmed by the significantly improved cell yields of L. delbrueckii subsp. bulgaricus when incubated in milk supplemented with adenine and guanine. The L. delbrueckii subsp. bulgaricus-expressed proteome in milk changed upon incubation at 4°C for 5 days and included increased levels of 17 proteins, several of which confer functions in stress tolerance (AddB, UvrC, RecA, and DnaJ). However, even with the activation of stress responses in either milk or MRS, L. delbrueckii subsp. bulgaricus did not survive passage through the murine digestive tract. These findings inform efforts to understand how L. delbrueckii subsp. bulgaricus is adapted to the dairy environment and its implications for its health-benefiting properties in the human digestive tract. IMPORTANCELactobacillus delbrueckii subsp. bulgaricus has a long history of use in yogurt production. Although commonly cocultured with Streptococcus salivarius subsp. thermophilus in milk, fundamental knowledge of the adaptive responses of L. delbrueckii subsp. bulgaricus to the dairy environment and the consequences of those responses on the use of L. delbrueckii subsp. bulgaricus as a probiotic remain to be elucidated. In this study, we identified proteins of L. delbrueckii subsp. bulgaricus LBB.B5 that are synthesized in higher quantities in milk at growth-conducive and non-growth-conductive (refrigeration) temperatures compared to laboratory culture medium and further examined whether those L. delbrueckii subsp. bulgaricus cultures were affected differently in their capacity to survive transit through the murine digestive tract. This work provides novel insight into how a major, food-adapted microbe responds to its primary habitat. Such knowledge can be applied to improve starter culture and yogurt production and to elucidate matrix effects on probiotic performance

HIV-1 Evolutionary Patterns Associated with Metastatic Kaposi's Sarcoma during AIDS.

Kaposi's sarcoma (KS) in HIV-infected individuals can have a wide range of clinical outcomes, from indolent skin tumors to a life-threatening visceral cancer. KS tumors contain endothelial-related cells and inflammatory cells that may be HIV-infected. In this study we tested if HIV evolutionary patterns distinguish KS tumor relatedness and progression. Multisite autopsies from participants who died from HIV-AIDS with KS prior to the availability of antiretroviral therapy were identified at the AIDS and Cancer Specimen Resource (ACSR). Two patients (KS1 and KS2) died predominantly from non-KS-associated disease and KS3 died due to aggressive and metastatic KS within one month of diagnosis. Skin and visceral tumor and nontumor autopsy tissues were obtained (n = 12). Single genome sequencing was used to amplify HIV RNA and DNA, which was present in all tumors. Independent HIV tumor clades in phylogenies differentiated KS1 and KS2 from KS3, whose sequences were interrelated by both phylogeny and selection. HIV compartmentalization was confirmed in KS1 and KS2 tumors; however, in KS3, no compartmentalization was observed among sampled tissues. While the sample size is small, the HIV evolutionary patterns observed in all patients suggest an interplay between tumor cells and HIV-infected cells which provides a selective advantage and could promote KS progression

Regression of Environmental Noise in LIGO Data

We address the problem of noise regression in the output of gravitational-wave (GW) interferometers, using data from the physical environmental monitors (PEM). The objective of the regression analysis is to predict environmental noise in the gravitational-wave channel from the PEM measurements. One of the most promising regression method is based on the construction of Wiener-Kolmogorov filters. Using this method, the seismic noise cancellation from the LIGO GW channel has already been performed. In the presented approach the Wiener-Kolmogorov method has been extended, incorporating banks of Wiener filters in the time-frequency domain, multi-channel analysis and regulation schemes, which greatly enhance the versatility of the regression analysis. Also we presents the first results on regression of the bi-coherent noise in the LIGO data

High-Resolution Molecular Epidemiology and Evolutionary History of HIV-1 Subtypes in Albania

HIV-1 epidemic in Western Europe is largely due to subtype B. Little is known about the HIV-1 in Eastern Europe, but a few studies have shown that non-B subtypes are quite common. In Albania, where a recent study estimated a ten-fold increase of AIDS incidence during the last six years, subtype A and B account for 90% of the know infections.We investigated the demographic history of HIV-1 subtype A and B in Albania by using a statistical framework based on coalescent theory and phylogeography. High-resolution phylogenetic and molecular clock analysis showed a limited introduction to the Balkan country of subtype A during the late 1980s followed by an epidemic outburst in the early 1990 s. In contrast, subtype B was apparently introduced multiple times between the mid-1970s and mid-1980s. Both subtypes are growing exponentially, although the HIV-1A epidemic displays a faster growth rate, and a significantly higher basic reproductive number R(0). HIV-1A gene flow occurs primarily from the capital Tirane, in the center of the country, to the periphery, while HIV-1B flow is characterized by a balanced exchange between center and periphery. Finally, we calculated that the actual number of infections in Albania is at least two orders of magnitude higher than previously thought.Our analysis demonstrates the power of recently developed computational tools to investigate molecular epidemiology of pathogens, and emphasize the complex factors involved in the establishment of HIV-1 epidemics. We suggest that a significant correlation exists between HIV-1 exponential spread and the socio-political changes occurred during the Balkan wars. The fast growth of a relatively new non-B epidemic in the Balkans may have significant consequences for the evolution of HIV-1 epidemiology in neighboring countries in Eastern and Western Europe

The global spread of Middle East respiratory syndrome: an analysis fusing traditional epidemiological tracing and molecular phylodynamics

Table S1. List of sequences used for analysis. Column “Label” corresponds to labels for sequences. presented in Figures 3 and 4 with country (by 2-letter ISO country code) and year of collection; countries, sources, and dates (month-year) are based on information in GenBank or related publication (indicated in Reference column). (DOCX 128 kb

PhyloTempo: A Set of R Scripts for Assessing and Visualizing Temporal Clustering in Genealogies Inferred from Serially Sampled Viral Sequences

Serially-sampled nucleotide sequences can be used to infer demographic history of evolving viral populations. The shape of a phylogenetic tree often reflects the interplay between evolutionary and ecological processes. Several approaches exist to analyze the topology and traits of a phylogenetic tree, by means of tree balance, branching patterns and comparative properties. The temporal clustering (TC) statistic is a new topological measure, based on ancestral character reconstruction, which characterizes the temporal structure of a phylogeny. Here, PhyloTempo is the first implementation of the TC in the R language, integrating several other topological measures in a user-friendly graphical framework. The comparison of the TC statistic with other measures provides multifaceted insights on the dynamic processes shaping the evolution of pathogenic viruses. The features and applicability of PhyloTempo were tested on serially-sampled intra-host human and simian immunodeficiency virus population data sets. PhyloTempo is distributed under the GNU general public license at https://sourceforge.net/projects/phylotempo/

Off-Adherence Keeping (OAK) observational study: intentional off-adherence immunomodulatory multiple sclerosis treatment

Aims: To evaluate how improved treatment adherence with a lower-frequency regimen/treatment of intramuscular (IM) IFN beta-1a impacts therapeutic effectiveness in relapsing-remitting multiple sclerosis (MS) patients switching from a higher-frequency injectable regimen/treatment. Patients & methods: Italian patients with relapsing-remitting MS and prior poor adherence to high-frequency injectable treatments (n = 181) were followed for 24 months after starting IM IFN beta-1a. Results: During the study, 97.4% of patients were treatment adherent; 22.1% of patients reported a relapse. The estimated probability of remaining relapse-free after 2 years was 78%. A high dropout rate (52.5%) led to small sample size and reduced statistical power. Conclusion: Intramuscular IFN beta-1a treatment was associated with high adherence and a low relapse rate. Unfortunately, low patient retention limited the generalizability of these findings.Plain language summary: Prior research suggests that taking the drug IFN beta-1a through less frequent muscle injections enables more patients to adhere to their prescription than taking other medications. This study included 181 Italian patients with relapsing-remitting multiple sclerosis (MS) who historically did not take medication as often as prescribed. Relapses of MS were counted among patients treated with muscle injections of IFN beta-1a for 2 years; 97.4% of patients followed their prescription and 22.1% experienced a relapse. From these data, 78% of patients were estimated not to experience a relapse during 2 years of IFN beta-1a muscle injections. However, an unusually high number of patients (52.5%) left the study within 2 years, which makes it difficult to draw firm conclusions

A Proposed Search for the Detection of Gravitational Waves from Eccentric Binary Black Holes

Most of compact binary systems are expected to circularize before the frequency of emitted gravitational waves (GWs) enters the sensitivity band of the ground based interferometric detectors. However, several mechanisms have been proposed for the formation of binary systems, which retain eccentricity throughout their lifetimes. Since no matched-filtering algorithm has been developed to extract continuous GW signals from compact binaries on orbits with low to moderate values of eccentricity, and available algorithms to detect binaries on quasi-circular orbits are sub-optimal to recover these events, in this paper we propose a search method for detection of gravitational waves produced from the coalescences of eccentric binary black holes (eBBH). We study the search sensitivity and the false alarm rates on a segment of data from the second joint science run of LIGO and Virgo detectors, and discuss the implications of the eccentric binary search for the advanced GW detectors