Efficient local strategies for vaccination and network attack

We study how a fraction of a population should be vaccinated to most efficiently top epidemics. We argue that only local information (about the neighborhood of specific vertices) is usable in practice, and hence we consider only local vaccination strategies. The efficiency of the vaccination strategies is investigated with both static and dynamical measures. Among other things we find that the most efficient strategy for many real-world situations is to iteratively vaccinate the neighbor of the previous vaccinee that has most links out of the neighborhood

Differences in the Pattern of Antibiotic Prescription Profile and Recurrence Rate for Possible Urinary Tract Infections in Women With and Without Diabetes

OBJECTIVE—Women with diabetes have a high incidence and complication rate of urinary tract infections (UTIs). Our aims were to compare current treatment strategies with respect to recurrence rates in women with diabetes with those without diabetes

Combinatorial activities of SHORT VEGETATIVE PHASE and FLOWERING LOCUS C define distinct modes of flowering regulation in Arabidopsis.

BACKGROUND: The initiation of flowering is an important developmental transition as it marks the beginning of the reproductive phase in plants. The MADS-box transcription factors (TFs) FLOWERING LOCUS C (FLC) and SHORT VEGETATIVE PHASE (SVP) form a complex to repress the expression of genes that initiate flowering in Arabidopsis. Both TFs play a central role in the regulatory network by conferring seasonal patterns of flowering. However, their interdependence and biological relevance when acting as a complex have not been extensively studied. RESULTS: We characterized the effects of both TFs individually and as a complex on flowering initiation using transcriptome profiling and DNA-binding occupancy. We find four major clusters regulating transcriptional responses, and that DNA binding scenarios are highly affected by the presence of the cognate partner. Remarkably, we identify genes whose regulation depends exclusively on simultaneous action of both proteins, thus distinguishing between the specificity of the SVP:FLC complex and that of each TF acting individually. The downstream targets of the SVP:FLC complex include a higher proportion of genes regulating floral induction, whereas those bound by either TF independently are biased towards floral development. Many genes involved in gibberellin-related processes are bound by the SVP:FLC complex, suggesting that direct regulation of gibberellin metabolism by FLC and SVP contributes to their effects on flowering. CONCLUSIONS: The regulatory codes controlled by SVP and FLC were deciphered at the genome-wide level revealing substantial flexibility based on dependent and independent DNA binding that may contribute to variation and robustness in the regulation of flowering

Continuous engagement of a self-specific activation receptor induces NK cell tolerance

Natural killer (NK) cell tolerance mechanisms are incompletely understood. One possibility is that they possess self-specific activation receptors that result in hyporesponsiveness unless modulated by self–major histocompatability complex (MHC)–specific inhibitory receptors. As putative self-specific activation receptors have not been well characterized, we studied a transgenic C57BL/6 mouse that ubiquitously expresses m157 (m157-Tg), which is the murine cytomegalovirus (MCMV)–encoded ligand for the Ly49H NK cell activation receptor. The transgenic mice were more susceptible to MCMV infection and were unable to reject m157-Tg bone marrow, suggesting defects in Ly49H+ NK cells. There was a reversible hyporesponsiveness of Ly49H+ NK cells that extended to Ly49H-independent stimuli. Continuous Ly49H–m157 interaction was necessary for the functional defects. Interestingly, functional defects occurred when mature wild-type NK cells were adoptively transferred to m157-Tg mice, suggesting that mature NK cells may acquire hyporesponsiveness. Importantly, NK cell tolerance caused by Ly49H–m157 interaction was similar in NK cells regardless of expression of Ly49C, an inhibitory receptor specific for a self-MHC allele in C57BL/6 mice. Thus, engagement of self-specific activation receptors in vivo induces an NK cell tolerance effect that is not affected by self-MHC–specific inhibitory receptors

Different gut microbial communities correlate with efficacy of albendazole-ivermectin against soil-transmitted helminthiases

Soil-transmitted helminth infections represent a large burden with over a quarter of the world's population at risk. Low cure rates are observed with standard of care (albendazole); therefore, a more effective combination therapy (albendazole and ivermectin) is being investigated but showed variable treatment efficacies without evidence of intrinsic parasite resistance. Here, we analyzed the microbiome of Trichuris trichiura and hookworm-infected patients and found an association of different enterotypes with treatment efficacy. 80 T. trichiura-infected patients with hookworm co-infections from Pak-Khan, Laos, received either albendazole (n = 41) or albendazole and ivermectin combination therapy (n = 39). Pre-/post-treatment stool samples were collected to monitor treatment efficacy and microbial communities were profiled using 16S rRNA gene sequencing, qPCR, and shotgun sequencing. We identified three bacterial enterotypes and show that pre-treatment enterotype is associated with efficacy of the combination treatment for both T. trichiura (CRET1 = 5.8%; CRET2 = 16.6%; CRET3 = 68.8%) and hookworm (CRET1 = 31.3%; CRET2 = 16.6%; CRET3 = 78.6%). This study shows that pre-treatment enterotype enables predicting treatment outcome of combination therapy for T. trichiura and hookworm infections.Trial registration: ClinicalTrials.gov, NCT03527732. Registered 17 May 2018, https://clinicaltrials.gov/ct2/show/NCT03527732

The use of typing methods and infection prevention measures to control a bullous impetigo outbreak on a neonatal ward

<p>Abstract</p> <p>Background</p> <p>We describe an outbreak of Bullous Impetigo (BI), caused by a (methicillin susceptible, fusidic acid resistant) <it>Staphylococcus aureus</it> (SA) strain, <it>spa-</it>type t408, at the neonatal and gynaecology ward of the Jeroen Bosch hospital in the Netherlands, from March-November 2011.</p> <p>Methods</p> <p>We performed an outbreak investigation with revision of the hygienic protocols, MSSA colonization surveillance and environmental sampling for MSSA including detailed typing of <it>SA</it> isolates. <it>Spa</it> typing was performed to discriminate between the SA isolates. In addition, Raman-typing was performed on all t408 isolates.</p> <p>Results</p> <p>Nineteen cases of BI were confirmed by SA positive cultures. A cluster of nine neonates and three health care workers (HCW) with <it>SA</it> t408 was detected. These strains were MecA^-, PVL^-, Exfoliative Toxin (ET)A^-, ETB⁺, ETAD^-, fusidic acid-resistant and methicillin susceptible. Eight out of nine neonates and two out of three HCW t408 strains yielded a similar Raman type. Positive t408 HCW were treated and infection control procedures were reinforced. These measures stopped the outbreak.</p> <p>Conclusions</p> <p>We conclude that treatment of patients and HCW carrying a predominant SA t408, and re-implementing and emphasising hygienic measures were effective to control the outbreak of SA t408 among neonates.</p