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This book links the molecular evolution of silk proteins to the evolution and behavioral ecology of web-spinning spiders and other arthropods. Craig ‘s book draws together studies from biochemistry through molecular genetics, cellular physiology, ecology, and behavior to present an integrated understanding of an interesting biological system at the molecular and organizational levels.

Spiders, objects of eternal human fascination, are found in many places: on the ground, in the air, and even under water. Leslie Brunetta and Catherine Craig have teamed up to produce a substantive yet entertaining book for anyone who has ever wondered, as a spider rappelled out of reach on a line of silk, \"How do they do that?\" The orb web, that iconic wheel-shaped web most of us associate with spiders, contains at least four different silk proteins, each performing a different function and all meshing together to create a fly-catching machine that has amazed and inspired humans through the ages. Brunetta and Craig tell the intriguing story of how spiders evolved over 400 million years to add new silks and new uses for silk to their survival \"toolkit\" and, in the telling, take readers far beyond the orb. The authors describe the trials and triumphs of spiders as they use silk to negotiate an ever-changing environment, and they show how natural selection acts at the genetic level and as individuals struggle for survival.

BackgroundChanges in invasive pneumococcal disease (IPD) incidence were evaluated after 7 years of 7-valent pneumococcal conjugate vaccine (PCV7) use in US children MethodsLaboratory-confirmed IPD cases were identified during 1998–2007 by 8 active population-based surveillance sites. We compared overall, age group-specific, syndrome-specific, and serotype group-specific IPD incidence in 2007 with that in 1998–1999 (before PCV7) and assessed potential serotype coverage of new conjugate vaccine formulations ResultsOverall and PCV7-type IPD incidence declined by 45% (from 24.4 to 13.5 cases per 100,000 population) and 94% (from 15.5 to 1.0 cases per 100,000 population), respectively (P<.01 for all age groups). The incidence of IPD caused by serotype 19A and other non-PCV7 types increased from 0.8 to 2.7 cases per 100,000 population and from 6.1 to 7.9 cases per 100,000 population, respectively (P<.01 for all age groups). The rates of meningitis and invasive pneumonia caused by non-PCV7 types increased for all age groups (P<.05), whereas the rates of primary bacteremia caused by these serotypes did not change. In 2006–2007, PCV7 types caused 2% of IPD cases, and the 6 additional serotypes included in an investigational 13-valent conjugate vaccine caused 63% of IPD cases among children <5 years-old ConclusionsDramatic reductions in IPD after PCV7 introduction in the United States remain evident 7 years later. IPD rates caused by serotype 19A and other non-PCV7 types have increased but remain low relative to decreases in PCV7-type IPD

Streptococcus pneumoniae is an important cause of bacterial meningitis. Since the introduction of the heptavalent pneumococcal conjugate vaccine PCV7, rates of pneumococcal meningitis have decreased substantially in the United States, from 1.13 cases to 0.79 case per 100,000 persons between 1998–1999 and 2004–2005; rates of disease from serotypes covered by the vaccine decreased the most, and rates from those not covered increased. Since the introduction of the heptavalent pneumococcal conjugate vaccine PCV7, rates of pneumococcal meningitis have decreased substantially in the United States, from 1.13 cases to 0.79 case per 100,000 persons between 1998–1999 and 2004–2005. Streptococcus pneumoniae is the most common cause of bacterial meningitis in the United States and many countries worldwide. 1 – 4 Despite effective antimicrobial therapy, pneumococcal meningitis remains highly lethal and has substantial long-term sequelae. 4 , 5 The pediatric heptavalent pneumococcal conjugate vaccine (PCV7; Prevnar, Wyeth) has had a major effect on the incidence of pneumococcal disease in the United States. 6 PCV7 not only protects immunized children from pneumococcal disease 7 – 11 but also provides protection to nonimmunized children and adults through herd immunity, resulting from reduced transmission of S. pneumoniae from immunized children. 8 , 10 , 12 , 13 Licensed in 2000, PCV7 is recommended by . . .

Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ and tissue regeneration remains unknown. EETs are produced predominantly in the endothelium. Normal organ and tissue regeneration require an active paracrine role of the microvascular endothelium, which in turn depends on angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate organ and tissue regeneration via production of bioactive EETs. To determine whether endothelial-derived EETs affect physiologic tissue growth in vivo, we used genetic and pharmacological tools to manipulate endogenous EET levels. We show that endothelial-derived EETs play a critical role in accelerating tissue growth in vivo, including liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. Administration of synthetic EETs recapitulated these results, whereas lowering EET levels, either genetically or pharmacologically, delayed tissue regeneration, demonstrating that pharmacological modulation of EETs can affect normal organ and tissue growth. We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration. Thus, our observations indicate a central role for EETs in organ and tissue regeneration and their contribution to tissue homeostasis.

Major international projects are underway that are aimed at creating a comprehensive catalogue of all the genes responsible for the initiation and progression of cancer. These studies involve the sequencing of matched tumour-normal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds. The list includes many implausible genes (such as those encoding olfactory receptors and the muscle protein titin), suggesting extensive false-positive findings that overshadow true driver events. We show that this problem stems largely from mutational heterogeneity and provide a novel analytical methodology, MutSigCV, for resolving the problem. We apply MutSigCV to exome sequences from 3,083 tumour-normal pairs and discover extraordinary variation in mutation frequency and spectrum within cancer types, which sheds light on mutational processes and disease aetiology, and in mutation frequency across the genome, which is strongly correlated with DNA replication timing and also with transcriptional activity. By incorporating mutational heterogeneity into the analyses, MutSigCV is able to eliminate most of the apparent artefactual findings and enable the identification of genes truly associated with cancer.

Penicillin allergy is one of the most commonly reported drug allergies, with a prevalence of 5% to 10%.2,3 The reported prevalence is higher among hospitalized patients, at 11% to 15%.4,5 Individuals with a history of penicillin hypersensitivity are more likely to receive alternative antibiotic therapy, which can lead to added expense, lengthened hospital stays, and increased risk for resistant organisms such as vancomycin-resistant Enterococcus, Clostridium difficile, and methicillin-resistant Staphylococcus aureus.6,7 Despite the frequency of reported allergy, avoidance of penicillin is not necessary in the vast majority of individuals. Approximately 90% to 95% of patients with a reported penicillin allergy can tolerate a rechallenge after an appropriate allergy evaluation has been performed.8,9 The discrepancy between reported and actual penicillin allergy may be explained by the waning of penicillin IgE antibodies over time or by the misclassification of an adverse reaction or infectious manifestation as a drug reaction.10-12 Sensitization to penicillin has been reported to decrease every 10 years, and after 20 years fewer than 1% of patients with initial clinical symptoms compatible with an allergic reaction continue to maintain their sensitivity. [...]a formal allergy evaluation is recommended by both North American and European guidelines to optimize patient management.13-15Major symptoms of hypersensitivity Hypersensitivity reactions to penicillin are classifiable as immediate or nonimmediate according to their clinical manifestation, time since the last drug administration, and the onset of symptoms.16,17 Immediate reactions are predominantly IgE-mediated. Skin testing and in vitro testing have been developed to identify a sensitization to a major/minor determinant and/or side chain and decrease the risk for a positive drug challenge test result.Penicillin skin testing For patients with a history concerning for an IgE-mediated reaction to penicillin, or whose past history is unclear, American and European guidelines recommend skin testing with both major penicillin antigenic determinants (penicilloyl-polylysine [PPL]) and minor antigenic determinants (benzylpenicillin [penicillin G], benzylpenicilloate, and benzylpenilloate).13,15,23 In the United States, penicillin G is the only commercially available minor determinant, and it is used in combination with PPL (PRE-PEN; AllerQuest LLC, West Hartford, Conn), whereas in Europe, benzylpenicilloyl-octa-l-lysine and sodium benzylpenilloate (DAP; Diater, Madrid, Spain) are available as major and minor determinant, respectively.8 It has been estimated that skin testing with PPL and penicillin G, without the use of penilloate and penicilloate, may miss 10% to 20% of penicillin-sensitized subjects.8,9,24-30 The clinical utility of penilloate and penicilloate is controversial because studies from North America have found a comparable negative predictive value (>95%) between skin testing to PPL and penicillin G only versus PPL and minor determinant mixture reagent in patients challenged to penicillin. [...]it is not possible to compare the negative predictive value.

Disparities in sexually transmitted infections (STI) are an urgent problem among Native American youth and young adults which are not fully explained by different sexual or related behaviors. These sexual health disparities are more likely attributed to social environments and structural determinants such as a shortage of sexual healthcare providers, lower socioeconomic status, and access barriers to STI screening and treatment, including geographic isolation and confidentiality concerns. Innovative, non-clinic based alternatives to promote STI screening and treatment are essential for alleviating these disparities. Self-care, or the care taken by individuals towards their own health and well-being may be such a strategy. This study will assess the efficacy of a self-care intervention, called Protecting Our Future Generation, for increasing uptake of STI screening and impacting sexual risk and protective behaviors among Native American youth and young adults living in a reservation-based community in the Southwestern United States. The proposed study is a randomized controlled trial to test the efficacy of a self-care intervention compared to a control condition. Participants will be Native Americans ages 14-26 years old who have had vaginal or anal sex at least once in their lifetime. Participants will be randomized to the intervention which includes: 1) a sexual health self-assessment with embedded clinical prediction tool predicting STI positivity, and 2) personalized messaging with key steps to lower risk for STIs, or the control condition which includes: 1) a self-assessment about water, soda and sugar sweetened beverage consumption, and 2) personalized messaging to meet recommended daily intake. All participants will be offered a self-administered STI test. Participants will complete assessments at baseline, 3- and 6-months follow-up. The primary outcome measure is completion of STI screening. Protecting Our Future Generation is among the first self-care interventions uniquely focused on sexual health among a Native American population, who endure significant sexual health disparities and are under-represented in research. If efficacious, the intervention will be a model of sexual health self-care for Native American youth and young adults adaptable for use in healthcare and community-based settings. Clinical Trials: http://clinicaltrials.gov; NCT03895320; Registered 03/28/2019.

Quantum many-body systems display rich phase structure in their low-temperature equilibrium states . However, much of nature is not in thermal equilibrium. Remarkably, it was recently predicted that out-of-equilibrium systems can exhibit novel dynamical phases that may otherwise be forbidden by equilibrium thermodynamics, a paradigmatic example being the discrete time crystal (DTC) . Concretely, dynamical phases can be defined in periodically driven many-body-localized (MBL) systems via the concept of eigenstate order . In eigenstate-ordered MBL phases, the entire many-body spectrum exhibits quantum correlations and long-range order, with characteristic signatures in late-time dynamics from all initial states. It is, however, challenging to experimentally distinguish such stable phases from transient phenomena, or from regimes in which the dynamics of a few select states can mask typical behaviour. Here we implement tunable controlled-phase (CPHASE) gates on an array of superconducting qubits to experimentally observe an MBL-DTC and demonstrate its characteristic spatiotemporal response for generic initial states . Our work employs a time-reversal protocol to quantify the impact of external decoherence, and leverages quantum typicality to circumvent the exponential cost of densely sampling the eigenspectrum. Furthermore, we locate the phase transition out of the DTC with an experimental finite-size analysis. These results establish a scalable approach to studying non-equilibrium phases of matter on quantum processors.