Articles de revues : « PhTAD »

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Stingley, Robin L., Barbara Brezna, Ashraf A. Khan et Carl E. Cerniglia. « Novel organization of genes in a phthalate degradation operon of Mycobacterium vanbaalenii PYR-1 ». Microbiology 150, n^o 11 (1 novembre 2004) : 3749–61. http://dx.doi.org/10.1099/mic.0.27263-0.

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Mycobacterium vanbaalenii PYR-1 is capable of degrading polycyclic aromatic hydrocarbons (PAHs) to ring cleavage metabolites. This study identified and characterized a putative phthalate degradation operon in the M. vanbaalenii PYR-1 genome. A putative regulatory protein (phtR) was encoded divergently with five tandem genes: phthalate dioxygenase large subunit (phtAa), small subunit (phtAb), phthalate dihydrodiol dehydrogenase (phtB), phthalate dioxygenase ferredoxin subunit (phtAc) and phthalate dioxygenase ferredoxin reductase (phtAd). A 6·7 kb EcoRI fragment containing these genes was cloned into Escherichia coli and converted phthalate to 3,4-dihydroxyphthalate. Homologues to the operon region were detected in a number of PAH-degrading Mycobacterium spp. isolated from various geographical locations. The operon differs from those of other Gram-positive bacteria in both the placement and orientation of the regulatory gene. In addition, the M. vanbaalenii PYR-1 pht operon contains no decarboxylase gene and none was identified within a 37 kb region containing the operon. This study is the first report of a phthalate degradation operon in Mycobacterium spp.

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Gul, Melek, Yiannis Elemes, Emel Pelit, Eleni Dernektsi, Dimitra Georgiou, Kosmas Oikonomou, Tadeusz Lis et Sławomir Szafert. « Synthesis of PhTAD-substituted dihydropyrrole derivatives via stereospecific C–H amination ». Research on Chemical Intermediates 43, n^o 2 (10 août 2016) : 1031–45. http://dx.doi.org/10.1007/s11164-016-2681-x.

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Kawaguchiya, Urushibara, Aung, Shinagawa, Takahashi et Kobayashi. « Prevalence of Various Vaccine Candidate Proteins in Clinical Isolates of Streptococcus pneumoniae : Characterization of the Novel Pht Fusion Proteins PhtA/B and PhtA/D ». Pathogens 8, n^o 4 (24 septembre 2019) : 162. http://dx.doi.org/10.3390/pathogens8040162.

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Pneumococcal proteins unrelated to serotypes are considered to be candidates of antigens in next-generation vaccines. In the present study, the prevalence of vaccine candidate protein genes, along with serotypes and antimicrobial resistance determinants, was investigated in a total of 57 isolates obtained from a tertiary care hospital in Japan. All of the pediatric isolates and 76.6% of the adult isolates did not belong to PCV13 (a 13-valent pneumococcal conjugate vaccine) serotypes, and 70.2% of all isolates showed multidrug resistance. All of the isolates had ply, pavA, nanA, and nanB, and high prevalence was noted for the pspA and pspC genes (96.5% and 78.9%, respectively). Detection rates for the pneumococcal histidine triad protein (Pht) genes phtA, phtB, phtD, and phtE were 49.1%, 26.3%, 61.4%, and 100%, respectively. Two fusion-type genes, phtA/B and phtA/D, were identified, with a prevalence of 36.9% and 14.0%, respectively. These fusion types showed 78.1–90.0% nucleotide sequence identity with phtA, phtB, and phtD. The most prevalent pht profile was phtA + phtD + phtE (26.3%), followed by phtA/B + phtE (19.3%) and phtA/B + phtD + phtE (17.5%), while pht profiles including phtD and/or phtA/phtD were found in 71.9% of isolates. The present study revealed the presence of two fusion types of Pht and their unexpectedly high prevalence. These fusion types, as well as PhtA and PhtB, contained sequences similar to the B cell epitopes that have been previously reported for PhtD.

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YAZGAN, Burak, Seda MESCİ, Masuk AKSAHIN, Arif AYAR, Melek GÜL et Tuba YILDIRIM. « PhTAD-Substituted Dihydropyrrole Compounds Regulate Apoptotic Cell Death in MCF-7 Cells ». Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi 14, n^o 2 (31 août 2021) : 737–50. http://dx.doi.org/10.18185/erzifbed.894125.

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Adamou, John E., Jon H. Heinrichs, Alice L. Erwin, William Walsh, Tony Gayle, Melissa Dormitzer, Ron Dagan et al. « Identification and Characterization of a Novel Family of Pneumococcal Proteins That Are Protective against Sepsis ». Infection and Immunity 69, n^o 2 (1 février 2001) : 949–58. http://dx.doi.org/10.1128/iai.69.2.949-958.2001.

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ABSTRACT Four pneumococcal genes (phtA, phtB, phtD, andphtE) encoding a novel family of homologous proteins (32 to 87% identity) were identified from the Streptococcus pneumoniae genomic sequence. These open reading frames were selected as potential vaccine candidates based upon their possession of hydrophobic leader sequences which presumably target these proteins to the bacterial cell surface. Analysis of the deduced amino acid sequences of these gene products revealed the presence of a histidine triad motif (HxxHxH), termed Pht (pneumococcal histidine triad) that is conserved and repeated several times in each of the four proteins. The four pht genes (phtA, phtB, phtD, and a truncated version of phtE) were expressed inEscherichia coli. A flow cytometry-based assay confirmed that PhtA, PhtB, PhtD and, to a lesser extent, PhtE were detectable on the surface of intact bacteria. Recombinant PhtA, PhtB, and PhtD elicited protection against certain pneumococcal capsular types in a mouse model of systemic disease. These novel pneumococcal antigens may serve as effective vaccines against the most prevalent pneumococcal serotypes.

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Rioux, Stéphane, Cécile Neyt, Emmanuel Di Paolo, Laurence Turpin, Nathalie Charland, Steve Labbé, Marie-Cécile Mortier et al. « Transcriptional regulation, occurrence and putative role of the Pht family of Streptococcus pneumoniae ». Microbiology 157, n^o 2 (1 février 2011) : 336–48. http://dx.doi.org/10.1099/mic.0.042184-0.

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Restricted to the genus Streptococcus, the Pht protein family comprises four members: PhtA, PhtB, PhtD and PhtE. This family has the potential to provide a protein candidate for incorporation in pneumococcal vaccines. Based on sequence analysis and on RT-PCR experiments, we show here that the pht genes are organized in tandem but that their expression, except that of phtD, is monocistronic. PhtD, PhtE, PhtB and PhtA are present in 100, 97, 81 and 62 % of the strains, respectively, and, by analysing its sequence conservation across 107 pneumococcal strains, we showed that PhtD displays very little variability. To analyse the physiological function of these proteins, several mutants were constructed. The quadruple Pht-deficient mutant was not able to grow in a poor culture medium, but the addition of Zn2+ or Mn2+ restored its growth capacity. Moreover, the phtD mRNA expression level increased when the culture medium was depleted in zinc. Therefore, we suggest that these proteins are zinc and manganese scavengers, and are able to store these metals and to release them when the bacterium faces an ion-restricted environment. The data also showed that this protein family, and more particularly PhtD, is a promising candidate to be incorporated into pneumococcal vaccines.

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Kallio, Anna, Kirsi Sepponen, Philippe Hermand, Philippe Denoël, Fabrice Godfroid et Merit Melin. « Role of Pht Proteins in Attachment of Streptococcus pneumoniae to Respiratory Epithelial Cells ». Infection and Immunity 82, n^o 4 (3 février 2014) : 1683–91. http://dx.doi.org/10.1128/iai.00699-13.

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ABSTRACTPneumococcal adherence to mucosal surfaces is a critical step in nasopharyngeal colonization, but so far few pneumococcal adhesins involved in the interaction with host cells have been identified. PhtA, PhtB, PhtD, and PhtE are conserved pneumococcal surface proteins that have proven promising as vaccine candidates. One suggested virulence function of Pht proteins is to mediate adherence at the respiratory mucosa. In this study, we assessed the role of Pht proteins in pneumococcal binding to respiratory epithelial cells. Pneumococci were incubated with human nasopharyngeal epithelial cells (Detroit-562) and lung epithelial cells (A549 and NCI-H292), and the proportion of bound bacteria was measured by plating viable counts. Strains R36A (unencapsulated), D39 (serotype 2), 43 (serotype 3), 4-CDC (serotype 4), and 2737 (serotype 19F) with one or more of the four homologous Pht proteins deleted were compared with their wild-type counterparts. Also, the effect of anti-PhtD antibodies on the adherence of strain 2737 to the respiratory epithelial cells was studied. Our results suggest that Pht proteins play a role in pneumococcal adhesion to the respiratory epithelium. We also found that antibody to PhtD is able to inhibit bacterial attachment to the cells, suggesting that antibodies against PhtD present at mucosal surfaces might protect from pneumococcal attachment and subsequent colonization. However, the relative significance of Pht proteins to the ability of pneumococci to bindin vitroto epithelial cells depends on the genetic background and the capsular serotype of the strain.

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Plumptre, Charles D., Abiodun D. Ogunniyi et James C. Paton. « Surface Association of Pht Proteins of Streptococcus pneumoniae ». Infection and Immunity 81, n^o 10 (22 juillet 2013) : 3644–51. http://dx.doi.org/10.1128/iai.00562-13.

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ABSTRACTStreptococcus pneumoniaeis a major human pathogen responsible for massive global morbidity and mortality. The pneumococcus attaches a variety of proteins to its cell surface, many of which contribute to virulence; one such family are the polyhistidine triad (Pht) proteins PhtA, PhtB, PhtD, and PhtE. In this study, we have examined the mechanism of Pht surface attachment using PhtD as a model. Analysis of deletion and point mutants identified a three-amino-acid region of PhtD (Q27-H28-R29) that is critical for the process. The analogous region in PhtE was also necessary for its attachment to the cell surface. Furthermore, we show that a large proportion of the total amount of each Pht protein is released into bacterial culture supernatants. Other surface proteins were also released, albeit to lesser extents, and this was not due to pneumococcal autolysis. The extent of release of surface proteins was strain dependent and was not affected by the capsule. Lastly, we compared the fitness of wild-type and ΔphtABDEpneumococciin vivoin a mouse coinfection model. Release of Pht proteins by the wild type did not complement the mutant strain, consistent with surface-attached rather than soluble forms of the Pht proteins playing the major role in virulence. The significant degree of release of Pht proteins from intact bacteria may have implications for the use of these proteins in novel vaccines.

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Malekan, Mohammadali, Seyed Davar Siadat, Mohammadreza Aghasadeghi, Nader Shahrokhi, Parviz Afrough, Ava Behrouzi, Khadijeh Ahmadi et Seyed Fazlollah Mousavi. « Evaluation of protective immunity responses against pneumococcal PhtD and its C-terminal in combination with outer-membrane vesicles as adjuvants ». Journal of Medical Microbiology 69, n^o 3 (1 mars 2020) : 465–77. http://dx.doi.org/10.1099/jmm.0.001103.

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Introduction. Streptococcus pneumoniae is a significant bacterial pathogen in humans. Currently, there are two types of pneumococcal vaccines, but there are concerns regarding their application. Aim. Since many pneumococcal proteins are serotype-independent, polyhistidine triad protein D (PhtD) has been selected as a vaccine candidate. Methodology. We prepared recombinant PhtD and its C-terminal fragment (PhtD-C) using alum and outer-membrane vesicles (OMVs) as adjuvants. The combinations were injected intraperitoneally into mice, and then total immunoglobulin G (IgG) and specific IgG, IgG1 and IgG2a were measured. A serum bactericidal assay and opsonophagocytosis were also performed as complementary tests. Meningococcal OMVs were used as an adjuvant. Results. The levels of specific IgG and IgG1 against combinations of PhtD and its C-terminal with OMVs and alum as adjuvants increased at the time of the third mouse immunization on day 35. Forty per cent and 60% of S. pneumoniae ATCC 6303 (serotype 3) as a virulent pneumococcal strain, respectively, were killed in the opsonophagocytosis test and these results could also be observed in the serum bactericidal assay. Mice mmunized iwith PhtD and its C-terminal with OMVs and alum as adjuvants survived after 10 days of pneumococcal challenge. Conclusion. The combination of PhtD and PhtD-C with alum produced optimal results, but the combination of PhtD and PhtD-C with OMVs produced minimal results by comparison. The survival rates were also measured, and these corresponded with the results of the immunological assessments. Our findings showed that mice receiving PhtD and PhtD-C plus OMV and alum had higher survival rates than the mice in the other groups.

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Mahawar, Krishna. « A LIVING TEMPLE - (PHAD PAINTING IN RAJASTHAN) ». International Journal of Research -GRANTHAALAYAH 6, n^o 3 (31 mars 2018) : 252–55. http://dx.doi.org/10.29121/granthaalayah.v6.i3.2018.1521.

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I consider Phad Painting as a valuable pilgrimage of Rajasthan. Phad painting (Mewar Style of painting) or Phad is a stye religious scroll painting and folk painting, practiced in Rajasthan state of India. This is a unique scroll making folk art; this style of painting is traditionally done on a long piece of cloth or canvas, known as phad. It is synonymous with the Bhopa community of the state. These are beautiful specimen of the Rajasthani cloth paintings. The narratives of the folk deities of Rajasthan, mostly of Pabuji and Devnarayan- who are worshipped as the incarnation of lord Vishnu & Laxman. Each hero-god has a different performer-priest or Bhopa. The repertoire of the bhopas consists of epics of some of the popular local hero-gods such as Pabuji, Devji, Tejaji, Gogaji, Ramdevji.The Phad also depict the lives of Ramdev Ji, Rama, Krishna, Budhha & Mahaveera. The iconography of these forms has evolved in a distinctive way. Shahpura in Bhilwara district of Rajasthan are widely known as the traditional artists of this folk art-form for the last two centuries. Presently, Shree Lal Joshi, Nand Kishor Joshi, Prakash Joshi and Shanti Lal Joshi are the most noted artists of the phad painting, who are known for their innovations and creativity. Noted examples of this art are Devnarayan Ki Phad and Pabuji Ki Phad.

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Sharma, Vishal, Hani J. Kbashi et Sergey Sergeyev. « MIMO-employed coherent photonic-radar (MIMO-Co-PHRAD) for detection and ranging ». Wireless Networks 27, n^o 4 (26 mars 2021) : 2549–58. http://dx.doi.org/10.1007/s11276-021-02605-2.

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AbstractRecently, the photonics-radar technology comes out as an attractive candidate in the arena of smart autonomous transportation, surveillance, and navigation-related applications owing to provide wide-spectra to attain improved and precise radar-resolutions. On the other hand, microwave radars, due to limited bandwidth, are incapable of coping with the demands of next-generation radar technology. Moreover, the atmospheric fluctuations become more prominent at higher frequencies and affect the radar’s performance significantly. Subsequently, the authors develop a 2 × 2 multi-input multi-output (MIMO) employed linear frequency-modulated continuous-wave coherent photonic-radar system (MIMO-Co-PHRAD) using OptiSystem™ and MATLAB™ to attain a prolonged detection-range with an enhanced visibility. The developed MIMO-Co-PHRAD is investigated with heterodyne- and homodyne-detection approaches under weak-to-strong regimes of the atmospheric fluctuations like Rain and Fog. A comparison is also drawn for both the demonstrated MIMO-equipped laser-driven coherent photonic-radar systems. The performance of both the developed MIMO-Co-PHRAD systems is evaluated by measuring the intensity of reflected-echoes, signal-to-noise ratio, and range-Doppler patterns. A contrast with the single-input single-output coherent photonic-radar (SISO-Co-PHRAD) is also established to validate the robustness of the demonstrated MIMO-Co-PHRAD.

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Pauksens, Karlis, Anna C. Nilsson, Magalie Caubet, Thierry G. Pascal, Pascale Van Belle, Jan T. Poolman, Pierre G. Vandepapelière, Vincent Verlant et Peter E. Vink. « Randomized Controlled Study of the Safety and Immunogenicity of Pneumococcal Vaccine Formulations Containing PhtD and Detoxified Pneumolysin with Alum or Adjuvant System AS02Vin Elderly Adults ». Clinical and Vaccine Immunology 21, n^o 5 (5 mars 2014) : 651–60. http://dx.doi.org/10.1128/cvi.00807-13.

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ABSTRACTSix vaccine formulations containing AS02Vor alum (aluminum phosphate [AlPO4]) adjuvant with pneumococcal proteins, pneumococcal histidine triad D (PhtD), and/or detoxified pneumolysin (dPly), either as a polysaccharide carrier in an 8-valent pneumococcal conjugate vaccine (8PCV) or as free (unconjugated) proteins, were evaluated in adults -65 to 85 years of age. In this phase I observer-blind study, 167 healthy subjects were randomized to receive two doses (days 0 and 60) of 10 or 30 μg PhtD-dPly plus AS02Vor alum, 8PCV plus AS02Vor alum, or one dose (day 0) of 23-valent polysaccharide pneumococcal vaccine (23PPV) as a control (placebo on day 60). The safety, reactogenicity, and antibody-specific responses to these vaccines were evaluated. No vaccine-related serious adverse events were reported. The incidences of solicited local and specific general (fatigue and myalgia) symptoms tended to be higher in the AS02Vgroups than in other groups. Anti-PhtD and anti-Ply antibody responses were observed in all groups except the control group. One month post-dose 2, the anti-PhtD and anti-Ply antibody geometric mean concentrations tended to be higher with AS02Vthan with alum, higher with a dose of 30 μg than with 10 μg for PhtD-dPly and higher with 30-μg PhtD-dPly formulations than with conjugated PhtD and dPly (8PCV) formulations. Functional antibody responses, measured by an opsonophagocytic activity assay, tended to be higher with 8PCV than with 23PPV. In conclusion, vaccine formulations containing free or conjugated PhtD and dPly had acceptable reactogenicity and safety profiles in elderly adults. Immune responses were enhanced with an AS02V-adjuvanted formulation containing free 30-μg PhtD-dPly compared to those with alum adjuvant and conjugated proteins. (This study has been registered atClinicalTrials.govunder registration no. NCT00756067.)

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Kaur, Ravinder, Naveen Surendran, Martina Ochs et Michael E. Pichichero. « Human Antibodies to PhtD, PcpA, and Ply Reduce Adherence to Human Lung Epithelial Cells and Murine Nasopharyngeal Colonization by Streptococcus pneumoniae ». Infection and Immunity 82, n^o 12 (22 septembre 2014) : 5069–75. http://dx.doi.org/10.1128/iai.02124-14.

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ABSTRACTStreptococcus pneumoniaeadherence to human epithelial cells (HECs) is the first step in pathogenesis leading to infections. We sought to determine the role of human antibodies againstS. pneumoniaeprotein vaccine candidates PhtD, PcpA, and Ply in preventing adherence to lung HECsin vitroand mouse nasopharyngeal (NP) colonizationin vivo. Human anti-PhtD, -PcpA, and -Ply antibodies were purified and Fab fragments generated. Fabs were used to test inhibition of adherence of TIGR4 and nonencapsulated strain RX1 to A549 lung HECs. The roles of individual proteins in adherence were tested using isogenic mutants of strain TIGR4. Anti-PhtD, -PcpA, and -Ply human antibodies were assessed for their ability to inhibit NP colonizationin vivoby passive transfer of human antibody in a murine model. Human antibodies generated against PhtD and PcpA caused a decrease in adherence to A549 cells (P< 0.05). Anti-PhtD but not anti-PcpA antibodies showed a protective role against mouse NP colonization. To our surprise, anti-Ply antibodies also caused a significant (P< 0.05) reduction inS. pneumoniaecolonization. Our results support the potential of PhtD, PcpA, and Ply protein vaccine candidates as alternatives to conjugate vaccines to prevent non-serotype-specificS. pneumoniaecolonization and invasive infection.

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Holmlund, Emma, Beatriz Quiambao, Jukka Ollgren, Teija Jaakkola, Cécile Neyt, Jan Poolman, Hanna Nohynek et Helena Käyhty. « Antibodies to Pneumococcal Proteins PhtD, CbpA, and LytC in Filipino Pregnant Women and Their Infants in Relation to Pneumococcal Carriage ». Clinical and Vaccine Immunology 16, n^o 6 (29 avril 2009) : 916–23. http://dx.doi.org/10.1128/cvi.00050-09.

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ABSTRACTThis study focuses on the immunogenicity of the following three pneumococcal vaccine candidate proteins in Filipino infants, all inducing protection in animal models: pneumococcal histidine triad protein D (PhtD), choline binding protein A (CbpA), and the lysozyme LytC. The immunoglobulin G antibody concentrations to PhtD, its putative, protective, and exposed C-terminal fragment (PhtD C), CbpA, and LytC were measured by enzyme immunoassay in 52 serum samples from pregnant women, 39 cord blood samples, and consecutive serum samples (n= 263) from 52 newborns between 6 weeks and 10 months of age scheduled to be taken at six time points. A nasopharyngeal swab to detect pneumococcal carriage was taken parallel to the serum samples. The antibody concentrations in the cord blood samples were similar to those in the samples from the mothers. In infant sera, the geometric mean antibody concentrations (GMCs) for all three proteins decreased until the age of 18 weeks and started to increase after that age, suggesting that the infants' own antibody production started close to the age of 4 to 5 months. The increase in GMCs by age, most clear-cut for CbpA, was associated with pneumococcal carriage. Anti-PhtD concentrations were higher than anti-PhtD C concentrations but correlated well (rof 0.89 at 10.5 months), suggesting that antibodies are directed to the supposedly exposed and protective C-terminal part of PhtD. Our results show that young children are able to develop an antibody response to PhtD, CbpA, and LytC and encourage the development of pneumococcal protein vaccines for this age group.

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Khan, M. N., et M. E. Pichichero. « CD4 T Cell Memory and Antibody Responses Directed against the Pneumococcal Histidine Triad Proteins PhtD and PhtE following Nasopharyngeal Colonization and Immunization and Their Role in Protection against Pneumococcal Colonization in Mice ». Infection and Immunity 81, n^o 10 (29 juillet 2013) : 3781–92. http://dx.doi.org/10.1128/iai.00313-13.

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ABSTRACTThe present study was undertaken to understand the role of vaccine candidates PhtD and PhtE in pneumococcal nasopharyngeal (NP) colonization, their ability to induce CD4 T cell memory and antibody responses following primary NP colonization, and their contribution to protection against secondary pneumococcal colonization in mice. The study was also aimed at understanding the potential of immunization with PhtD and PhtE in eliciting qualitative CD4 T cell memory responses and protection against pneumococcal NP colonization in mice. PhtD and PhtE isogenic mutants in a TIGR4 background (TIGR4 ΔPhtD and TIGR4 ΔPhtE) were constructed and found to have a significantly reduced colonization density over time in the nasopharynges of mice compared to those of mice colonized with wild-type TIGR4. Mice with primary colonization by wild-type TIGR4, TIGR4 ΔPhtD, or TIGR4 ΔPhtE were protected against secondary colonization by wild-type TIGR4; nonetheless, the clearance of secondary colonization was slower in mice with primary colonization by either TIGR4 ΔPhtD or TIGR4 ΔPhtE than in mice with primary colonization by wild-type TIGR4. Colonization was found to be an immunizing event for PhtD and PhtE antigens (antibody response); however, we failed to detect any antigen (PhtD or PhtE)-specific CD4 T cell responses in any of the colonized groups of mice. Intranasal immunization with either PhtD or PhtE protein generated robust serum antibody and CD4 Th1-biased immune memory and conferred protection against pneumococcal colonization in mice. We conclude that PhtD and PhtE show promise as components in next-generation pneumococcal vaccine formulations.

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Klinke, Stefan, Guy de Roo, Bernard Witholt et Birgit Kessler. « Role of phaD in Accumulation of Medium-Chain-Length Poly(3-Hydroxyalkanoates) inPseudomonas oleovorans ». Applied and Environmental Microbiology 66, n^o 9 (1 septembre 2000) : 3705–10. http://dx.doi.org/10.1128/aem.66.9.3705-3710.2000.

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ABSTRACT Pseudomonas oleovorans is capable of producing poly(3-hydroxyalkanoates) (PHAs) as intracellular storage material. To analyze the possible involvement of phaD in medium-chain-length (MCL) PHA biosynthesis, we generated aphaD knockout mutant by homologous recombination. Upon disruption of the phaD gene, MCL PHA polymer accumulation was decreased. The PHA granule size was reduced, and the number of granules inside the cell was increased. Furthermore, mutant cells appeared to be smaller than wild-type cells. Investigation of MCL PHA granules revealed that the pattern of granule-associated proteins was changed and that the predominant protein PhaI was missing in the mutant. Complementation of the mutant with a phaD-harboring plasmid partially restored the wild-type characteristics of MCL PHA production and fully restored the granule and cell sizes. Furthermore, PhaI was attached to the granules of the complemented mutant. These results indicate that the phaD gene encodes a protein which plays an important role in MCL PHA biosynthesis. However, although its main effect seems to be the stabilization of MCL PHA granules, we found that the PhaD protein is not a major granule-associated protein and therefore might act by an unknown mechanism involving the PhaI protein.

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Melin, Merit, Emmanuel Di Paolo, Leena Tikkanen, Hanna Jarva, Cecile Neyt, Helena Käyhty, Seppo Meri, Jan Poolman et Merja Väkeväinen. « Interaction of Pneumococcal Histidine Triad Proteins with Human Complement ». Infection and Immunity 78, n^o 5 (1 mars 2010) : 2089–98. http://dx.doi.org/10.1128/iai.00811-09.

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ABSTRACT The pneumococcal histidine triad (Pht) proteins PhtA, PhtB, PhtD, and PhtE form a group of conserved pneumococcal surface proteins. Humans produce antibodies to Pht proteins upon exposure to pneumococcus, and immunization of mice has provided protective immunity against sepsis and pneumonia and reduced nasopharyngeal colonization. Pht proteins are candidates for inclusion in multicomponent pneumococcal protein vaccines. Their biological function in pneumococcal infections is not clear, but a role in complement inhibition has been suggested. We measured complement deposition on wild-type and Pht mutant strains in four genetic backgrounds: Streptococcus pneumoniae D39 (serotype 2) and R36A (unencapsulated derivative of D39) and strains of serotypes 3, 4, and 19F. PspA and PspC single and double mutants were compared to the wild-type and Pht-deficient D39 strains. Factor H binding was measured to bacterial cells, lysates, and protein antigens. Deletion of all four Pht proteins (Pht−) resulted in increased C3 deposition on the serotype 4 strain but not on the other strains. Pht antigens did not bind factor H, and deletion of Pht proteins did not affect factor H binding by bacterial lysates. The Pht− mutant serotype 4 strain bound slightly less factor H than the wild-type strain when binding was measured by flow cytometry. Pht proteins may play a role in immune evasion, but the mechanism of function is unlikely to be mediated by factor H binding. The relative contribution of Pht proteins to the inhibition of complement deposition is likely to be affected by the presence of other pneumococcal proteins and to depend on the genetic background.

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Verhoeven, David, Sheldon Perry et Michael E. Pichichero. « Contributions to Protection from Streptococcus pneumoniae Infection Using the Monovalent Recombinant Protein Vaccine Candidates PcpA, PhtD, and PlyD1 in an Infant Murine Model during Challenge ». Clinical and Vaccine Immunology 21, n^o 8 (21 mai 2014) : 1037–45. http://dx.doi.org/10.1128/cvi.00052-14.

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ABSTRACTA vaccine consisting of several conserved proteins with different functions directing the pathogenesis of pneumonia and sepsis would be preferred for protection against infection byStreptococcus pneumoniae. Infants will be the major population targeted for next-generation pneumococcal vaccines. Here, we investigated the potential efficacy provided by three recombinant pneumococcal vaccine candidate proteins—pneumococcal histidine triad D (PhtD), detoxified pneumolysin derivative (PlyD1), and pneumococcal choline-binding protein A (PcpA)—for reducing pneumonia and sepsis in an infant mouse vaccine model. We found vaccination with PhtD and PcpA provided high IgG antibody titers after vaccination in infant mice, similar to adult mice comparators. PlyD1-specific total IgG was significantly lower in infant mice, with minimal boosting with the second and third vaccinations. Similar isotypes of IgG for PhtD and PlyD1 were generated in infant compared to adult mice. Although lower total specific IgG to all three proteins was elicited in infant than in adult mice, the infant mice were protected from bacteremic pneumonia and sepsis mortality (PlyD1) and had lower lung bacterial burdens (PcpA and PhtD) after challenge. The observed immune responses coupled with bacterial reductions elicited by each of the monovalent proteins support further testing in human infant clinical trials.

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Mousa, Jarrod J., Jiachen Huang, Aaron D. Gingerich, Fredejah Royer, Amy V. Paschall et Fikri Y. Avci. « Broadly reactive human antibodies prevent and treat pneumococcal infection ». Journal of Immunology 206, n^o 1_Supplement (1 mai 2021) : 59.16. http://dx.doi.org/10.4049/jimmunol.206.supp.59.16.

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Abstract Streptococcus pneumoniae remains a leading cause of bacterial pneumonia despite the widespread introduction of vaccines for disease prevention. While vaccines have been effective at reducing the incidence of most vaccine-included serotypes, a rise in infection due to non-vaccine serotypes, and moderate efficacy against some vaccine included serotypes have contributed to high disease incidence, particularly in the elderly. Additionally, numerous isolates of S. pneumoniae are antibiotic resistant or multi-drug resistant. Several highly conserved pneumococcal proteins that are prevalent in the majority of serotypes have been examined and tested as potential vaccines in preclinical and clinical trials. We isolated the first human monoclonal antibodies (mAbs) (PhtD3, PhtD6, PhtD7, PhtD8, PspA16) against the pneumococcal histidine triad protein (PhtD), and the pneumococcal surface protein A (PspA), two conserved and protective antigens. mAbs to PhtD target diverse epitopes spanning the entire PhtD protein, and mAb PspA16 targets the N-terminal segment of PspA. The PhtD-specific mAbs were found to bind to multiple serotypes, while PspA16 serotype breadth was limited. In addition, we examined the prophylactic and therapeutic efficacy of mAb PhtD3 in several mouse models of pneumococcal pneumonia and sepsis. mAb PhtD3 prolonged the survival of infected mice when administered 2 hours before infection or 24 hours after infection. Additionally, mAb PhtD3 was effective against pneumococcal serotypes 4 and 3, the latter of which is a leading cause of invasive pneumococcal disease. Overall, our results provide new therapeutic reagents for disease prevention, and identify regions on PhtD and PspA recognized by human B cells.

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Jiang, Kai, Di Zhao, Rui Ye, Xinlong Liu, Chao Gao, Yuanyuan Guo, Chuan Zhang, Jian Zeng, Shi Wang et Jie Song. « Transdermal delivery of poly-hyaluronic acid-based spherical nucleic acids for chemogene therapy ». Nanoscale 14, n^o 5 (2022) : 1834–46. http://dx.doi.org/10.1039/d1nr06353g.

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Li, Fengrong, Kaiyan Wang, Kunpeng Liu et Mahsa Ebrahimi. « The Application of Pelvic Floor Ultrasound Image Analysis Technology in the Neurorehabilitation of Postpartum Urinary Incontinence ». Journal of Medical Imaging and Health Informatics 11, n^o 2 (1 février 2021) : 618–22. http://dx.doi.org/10.1166/jmihi.2021.3330.

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Objective: To evaluate the outcome of neurorehabilitation on the structure of the pelvic floor muscle (PFM) of parturient women by using the image analysis technology of PFM ultrasonography, and to explore the imaging indexes for the comprehensive evaluation of the therapeutic outcome of postpartum urinary incontinence (PUI), thus providing a direct and reliable imaging basis for the clinic. Methods: From January 2017 to July 2019, 80 patients suffering from stress incontinence were included. All patients were divided into the control group (40 patients) and the rehabilitation group (40 patients) randomly. They received routine guidance, health education, and neurorehabilitation, respectively. The PFM was examined and the therapeutic outcome was evaluated by the PFM ultrasonography image analysis technology. Results: Compared to the control group, in the resting state, the levels of pelvic diaphragm hiatus diameter (PHD), pelvic diaphragm hiatus transverse diameter (PHTD), pelvic diaphragm hiatus area (PHA), and the horizontal angle of levator ani muscle (LAM) hiatus of the rehabilitation group were notably lower; in the maximum Valsalva action, the PHD, PHTD, and PHA levels of the rehabilitation group were notably lower; in the anorectal movement, the PHD, PHTD, and PHA levels of the rehabilitation group were notably decreased, and the total effectiveness of the rehabilitation group was notably higher. Conclusion: PFM ultrasonography image analysis technology can dynamically observe the changes of PFM structure parameters before and after neurorehabilitation, which is worthy of clinical application. PHD, PHTD and PHA can be used as important imaging indicators to measure the outcome of neurorehabilitation.

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Fonseca, Maris V., John-Demian Sauer, Sebastien Crepin, Brenda Byrne et Michele S. Swanson. « ThephtC-phtDLocus Equips Legionella pneumophila for Thymidine Salvage and Replication in Macrophages ». Infection and Immunity 82, n^o 2 (2 décembre 2013) : 720–30. http://dx.doi.org/10.1128/iai.01043-13.

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ABSTRACTThe phagosomal transporter (Pht) family of the major facilitator superfamily (MFS) is encoded by phylogenetically related intracellular gammaproteobacteria, including the opportunistic pathogenLegionella pneumophila. The location of thephtgenes between the putative thymidine kinase (tdk) and phosphopentomutase (deoB) genes suggested that thephtCandphtDloci contribute to thymidine salvage inL. pneumophila. Indeed, aphtC+allele intransrestored pyrimidine uptake to anEscherichia colimutant that lacked all known nucleoside transporters, whereas aphtD+allele did not. The results of phenotypic analyses ofL. pneumophilastrains lackingphtCorphtDstrongly indicate thatL. pneumophilarequires PhtC and PhtD function under conditions where sustained dTMP synthesis is compromised. First, in broth cultures that mimicked thymidine limitation or starvation,L. pneumophilaexhibited a marked requirement for PhtC function. Conversely, mutation ofphtDconferred a survival advantage. Second, in medium that lacked thymidine, multicopyphtC+orphtD+alleles enhanced the survival ofL. pneumophilathymidylate synthase (thyA)-deficient strains, which cannot synthesize dTMP endogenously. Third, under conditions in which transport of the pyrimidine nucleoside analog 5-fluorodeoxyuridine (FUdR) would inhibit growth, PhtC and PhtD conferred a growth advantage toL. pneumophilathyA+strains. Finally, when cultured in macrophages,L. pneumophilarequired thephtC-phtDlocus to replicate. Accordingly, we propose that PhtC and PhtD contribute to protectL. pneumophilafrom dTMP starvation during its intracellular life cycle.

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Godfroid, Fabrice, Philippe Hermand, Vincent Verlant, Philippe Denoël et Jan T. Poolman. « Preclinical Evaluation of the Pht Proteins as Potential Cross-Protective Pneumococcal Vaccine Antigens ». Infection and Immunity 79, n^o 1 (18 octobre 2010) : 238–45. http://dx.doi.org/10.1128/iai.00378-10.

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ABSTRACTCurrent pneumococcal vaccines are composed of capsular polysaccharides (PS) of various serotypes, either as free PS or as protein-PS conjugates. The use of pneumococcus protein antigens that are able to afford protection across the majority of serotypes is envisaged as a relevant alternative and/or complement to the polysaccharides. In this context, based on several studies, the Pht protein family emerged as relevant vaccine candidates. The purpose of the present study was to evaluate the Pht protein family in several preclinical mouse models. Immunization with these antigens was compared with immunization with other pneumococcal antigens, such as CbpA, PspA, and PsaA. In a nasopharyngeal colonization model and in a lung colonization model, the Phts were found to be superior to the other candidates in terms of efficacy of protection and serotype coverage. Likewise, vaccination with PhtD allowed higher animal survival rates after lethal intranasal challenge. Finally, a passive transfer model in which natural anti-PhtD human antibodies were transferred into mice demonstrated significant protection against lethal intranasal challenge. This indicates that natural anti-PhtD human antibodies are able to protect against pneumococcal infection. Our findings, together with the serotype-independent occurrence of the Phts, designate this protein family as valid candidate antigens to be incorporated in protein-based pneumococcal vaccines.

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Laattoe, Tariq, Vincent E. A. Post et Adrian D. Werner. « A Spatially Periodic Solute Boundary for MT3DMS and PHT3D ». Groundwater 55, n^o 3 (14 décembre 2016) : 419–27. http://dx.doi.org/10.1111/gwat.12490.

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Eijkelkamp, Bart A., Victoria G. Pederick, Charles D. Plumptre, Richard M. Harvey, Catherine E. Hughes, James C. Paton et Christopher A. McDevitt. « The First Histidine Triad Motif of PhtD Is Critical for Zinc Homeostasis inStreptococcus pneumoniae ». Infection and Immunity 84, n^o 2 (16 novembre 2015) : 407–15. http://dx.doi.org/10.1128/iai.01082-15.

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Streptococcus pneumoniaeis the world's foremost human pathogen. Acquisition of the first row transition metal ion zinc is essential for pneumococcal colonization and disease. Zinc is acquired via the ATP-binding cassette transporter AdcCB and two zinc-binding proteins, AdcA and AdcAII. We have previously shown that AdcAII is reliant upon the polyhistidine triad (Pht) proteins to aid in zinc recruitment. Pht proteins generally contain five histidine (His) triad motifs that are believed to facilitate zinc binding and therefore play a significant role in pneumococcal metal ion homeostasis. However, the importance and potential redundancy of these motifs have not been addressed. We examined the effects of mutating each of the five His triad motifs of PhtD. The combination ofin vitrogrowth assays, active zinc uptake, and PhtD expression studies show that the His triad closest to the protein's amino terminus is the most important for zinc acquisition. Intriguingly,in vivocompetitive infection studies investigating the amino- and carboxyl-terminal His triad mutants indicate that the motifs have similar importance in colonization. Collectively, our new insights into the contributions of the individual His triad motifs of PhtD, and by extension the other Pht proteins, highlight the crucial role of the first His triad site in zinc acquisition. This study also suggests that the Pht proteins likely play a role beyond zinc acquisition in pneumococcal virulence.

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Sherif, El-Sayed M., et Asiful H. Seikh. « Effects of Immersion Time and 5-Phenyl-1H-tetrazole on the Corrosion and Corrosion Mitigation of Cobalt Free Maraging Steel in 0.5 M Sulfuric Acid Pickling Solutions ». Journal of Chemistry 2013 (2013) : 1–7. http://dx.doi.org/10.1155/2013/497823.

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The effect of exposure time and 5-phenyl-1H-tetrazole on the corrosion and corrosion mitigation of cobalt free maraging steel in 0.5 M H2SO4pickling solutions has been reported using electrochemical and spectroscopic investigations. Potentiodynamic polarization data showed that the increase of immersion time from 0 min to 120 min increases the corrosion rate and decreases the polarization resistance of the maraging steel. On the other hand, the addition of PHTA and the increase of its concentration decrease all the corrosion parameters of the steel at all exposure test periods. Electrochemical impedance spectroscopy measurements agreed with the obtained polarization data. Scanning electron spectroscopy and energy dispersive X-ray investigations confirmed that the inhibition of the steel corrosion is achieved via the adsorption of the PHTA molecules onto the steel precluding its surface from being dissolved.

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Tummala, Seshu B., Neil E. Welker et Eleftherios T. Papoutsakis. « Development and Characterization of a Gene Expression Reporter System for Clostridium acetobutylicumATCC 824 ». Applied and Environmental Microbiology 65, n^o 9 (1 septembre 1999) : 3793–99. http://dx.doi.org/10.1128/aem.65.9.3793-3799.1999.

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ABSTRACT A gene expression reporter system (pHT3) for Clostridium acetobutylicum ATCC 824 was developed by using thelacZ gene from Thermoanaerobacterium thermosulfurogenes EM1 as the reporter gene. In order to test the reporter system, promoters of three key metabolic pathway genes,ptb (coding for phosphotransbutyrylase), thl(coding for thiolase), and adc (coding for acetoacetate decarboxylase), were cloned upstream of the reporter gene in pHT3 in order to construct vectors pHT4, pHT5, and pHTA, respectively. Detection of β-galactosidase activity in time course studies performed with strains ATCC 824(pHT4), ATCC 824(pHT5), and ATCC 824(pHTA) demonstrated that the reporter gene produced a functional β-galactosidase in C. acetobutylicum. In addition, time course studies revealed differences in the β-galactosidase specific activity profiles of strains ATCC 824(pHT4), ATCC 824(pHT5), and ATCC 824(pHTA), suggesting that the reporter system developed in this study is able to effectively distinguish between different promoters. The stability of the β-galactosidase produced by the reporter gene was also examined with strains ATCC 824(pHT4) and ATCC 824(pHT5) by using chloramphenicol treatment to inhibit protein synthesis. The data indicated that the β-galactosidase produced by the lacZgene from T. thermosulfurogenes EM1 was stable in the exponential phase of growth. In pH-controlled fermentations of ATCC 824(pHT4), the kinetics of β-galactosidase formation from theptb promoter and phosphotransbutyrylase formation from its own autologous promoter were found to be similar.

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Appelo, C. A. J., et Massimo Rolle. « PHT3D : A Reactive Multicomponent Transport Model for Saturated Porous Media ». Ground Water 48, n^o 5 (16 juillet 2010) : 627–32. http://dx.doi.org/10.1111/j.1745-6584.2010.00732.x.

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Borges, Igor C., Dafne C. Andrade, Maria Regina A. Cardoso, Jorma Toppari, Mari Vähä-Mäkilä, Jorma Ilonen, Mikael Knip et al. « Natural Development of Antibodies against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis Protein Antigens during the First 13 Years of Life ». Clinical and Vaccine Immunology 23, n^o 11 (31 août 2016) : 878–83. http://dx.doi.org/10.1128/cvi.00341-16.

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ABSTRACTConserved protein antigens have been investigated as vaccine candidates against respiratory pathogens. We evaluated the natural development of antibodies againstStreptococcus pneumoniae,Haemophilus influenzae, andMoraxella catarrhalisproteins during childhood. Serum samples were collected from 50 healthy children from their first months to age 13 years (median sampling interval, 6 months). We also analyzed serum samples from 24 adults. Serum IgG antibodies against eight pneumococcal proteins (Ply, CbpA, PspA 1 and 2, PcpA, PhtD, StkP-C, and PcsB-N), threeH. influenzaeproteins, and fiveM. catarrhalisproteins were measured using a multiplexed bead-based immunoassay. Antibody levels were analyzed using multilevel mixed-effects regression and Spearman's correlation. Antibody levels against pneumococcal proteins peaked at 3 to 5 years of age and then reached a plateau. Antibody levels againstH. influenzaeproteins peaked during the second year and then stabilized. Antibody levels againstM. catarrhalisproteins peaked during the first year and then slowly decreased. Peak antibody levels during childhood were higher than those of adults. Correlations among pneumococcal antibody levels were highest among anti-CbpA, anti-PcpA, and anti-PhtD antibodies (r= 0.71 to 0.75;P< 0.001). The children presented 854 symptomatic respiratory infections on 586 occasions. Symptomatic respiratory infections did not improve prediction of antibody levels in the regression model. The maturation of immune responses against the investigated pneumococcal proteins shares similarities, especially among CbpA, PcpA, and PhtD. Antibody production againstH. influenzaeandM. catarrhalisproteins starts early in life and reaches peak levels earlier than antibody production against the pneumococcal proteins. Basal antibody levels are not related to the occurrence of symptomatic respiratory infections.

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Berglund, Johan, Peter Vink, Fernanda Tavares Da Silva, Pascal Lestrate et Dominique Boutriau. « Safety, Immunogenicity, and Antibody Persistence following an Investigational Streptococcus pneumoniae and Haemophilus influenzae Triple-Protein Vaccine in a Phase 1 Randomized Controlled Study in Healthy Adults ». Clinical and Vaccine Immunology 21, n^o 1 (30 octobre 2013) : 56–65. http://dx.doi.org/10.1128/cvi.00430-13.

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ABSTRACTWe investigated a protein-based nontypeableHaemophilus influenzae(NTHi) and pneumococcal (HiP) vaccine containing pneumococcal histidine triad D (PhtD), detoxified pneumolysin (dPly), and NTHi protein D (PD) in adults. In a phase I study, 40 healthy 18- to 40-year-old subjects were randomized (2:2:1) to receive two HiP doses administered 60 days apart, with or without AS03 adjuvant (HiP-AS and HiP groups, respectively), or Engerix B (GlaxoSmithKline, Belgium) as a control. Safety, antibodies, and antigen-specific CD4+T-cell immune responses were assessed before and until 480 days after vaccination. No serious adverse events were reported, and no subject withdrew due to an adverse event. Local and systemic symptoms were reported more frequently in the HiP-AS group than in the other two groups. The frequency and intensity of local and systemic symptoms appeared to increase after the second dose of HiP-AS or HiP but not Engerix B. Antibody geometric mean concentrations (GMCs) for PhtD, dPly, and PD increased after each dose of HiP-AS or HiP, with higher GMCs being observed in the HiP-AS group (statistically significant for anti-PD after dose 1 and anti-Ply after dose 2). GMCs remained higher at day 420 than prior to vaccination in both the HiP-AS and HiP groups. Antigen-specific CD4+T cells increased after each dose but were unmeasurable by day 480. Two doses of an investigational PhtD-dPly-PD protein vaccine induced humoral immunity and antigen-specific CD4+T-cell responses after each dose, with generally higher responses when the vaccine was administered with AS03. HiP combined with AS03 appeared to be more reactogenic than the antigens alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT00814489.)

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Wu, Ming Zhi, Vincent E. A. Post, S. Ursula Salmon, Eric D. Morway et Henning Prommer. « PHT3D-UZF : A Reactive Transport Model for Variably-Saturated Porous Media ». Groundwater 54, n^o 1 (27 janvier 2015) : 23–34. http://dx.doi.org/10.1111/gwat.12318.

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Fang, Haiquan. « Semantic Segmentation of PHT Based on Improved DeeplabV3+ ». Mathematical Problems in Engineering 2022 (19 mars 2022) : 1–8. http://dx.doi.org/10.1155/2022/6228532.

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This work aimed to address the two shortcomings of the printed and handwritten texts (PHT) classification. The classification accuracy of FCN and U-net, which are used for PHT pixel-level classification, still has room to improve. PHT public datasets have small sample sizes, and the generalization ability of the models is not good. In this paper, first, a pixel-level sample-making method for PHT identification was proposed, and a PHT dataset 2021 (PHTD 2021), containing 3,000 samples, was constructed. Second, because there is a large number of words but the contours are small in documents, the DeeplabV3+ model was improved. The network layer number and pooling times were reduced, and the convolution kernel and dilated rate were increased. In the experiment, the improved DeeplabV3+ model had a classification accuracy of 95.06% on the test samples from the PHTD 2021 dataset. The improved DeeplabV3+ model has a higher recognition accuracy than the FCN and DeeplabV3+ models. Finally, after the classification of PHT, applications of handwritten texts removal and handwritten texts extraction are provided.

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Denoël, Philippe, Fabrice Godfroid, Philippe Hermand, Vincent Verlant et Jan Poolman. « Combined protective effects of anti-PhtD and anti-pneumococcal polysaccharides ». Vaccine 29, n^o 38 (septembre 2011) : 6451–53. http://dx.doi.org/10.1016/j.vaccine.2011.01.085.

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André, Greiciely O., Lucas Assoni, Dunia Rodriguez, Luciana C. C. Leite, Thaisy E. P. dos Santos, Lucio F. C. Ferraz, Thiago R. Converso et Michelle Darrieux. « Immunization with PhtD truncated fragments reduces nasopharyngeal colonization by Streptococcus pneumoniae ». Vaccine 38, n^o 26 (mai 2020) : 4146–53. http://dx.doi.org/10.1016/j.vaccine.2020.04.050.

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Simell, Birgit, Mika Lahdenkari, Antti Reunanen, Helena Käyhty et Merja Väkeväinen. « Effects of Ageing and Gender on Naturally Acquired Antibodies to Pneumococcal Capsular Polysaccharides and Virulence-Associated Proteins ». Clinical and Vaccine Immunology 15, n^o 9 (2 juillet 2008) : 1391–97. http://dx.doi.org/10.1128/cvi.00110-08.

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ABSTRACT Elderly individuals are susceptible to pneumococcal infections. Although factors contributing to the increased susceptibility of the elderly to bacterial infections may be several, compromised immune function, a consequence of normal human ageing, is widely accepted to play a role. We evaluated the effect of ageing on the concentrations of naturally acquired antibodies to pneumococcal capsular polysaccharides (PPS) and protein antigens. The concentrations of immunoglobulin G (IgG) and IgM antibodies to the PPS of serotypes 3, 4, 6B, 9V, 14, and 23F and IgG antibodies to the pneumococcal virulence-associated proteins CbpA, LytC, PhtD and its C-terminal fragment (PhtD C), NanA, PspA fam1, and PspA fam2 were measured by enzyme immunoassay in the sera of younger (30 to 64 years of age) and elderly (65 to 97 years of age) adults. The concentrations of anti-PPS IgG against serotypes 3 and 6B, of anti-PPS IgM against serotypes 3, 4, 6B, 9V, and 23F, and of anti-protein IgG against all tested antigens were significantly lower in the elderly than in younger adults. A stronger decline in anti-PPS antibody concentrations was seen with age in women compared to men, while anti-protein antibody concentrations were mainly similar between the genders. Age, gender, and the nature of the antigen have substantial and varying effects on the antibody concentrations in the sera of adults.

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Harberts, Erin M., Kelsey A. Gregg, Francesca M. Gardner, Mark R. Pelletier, Li Yu, Michael P. McCarthy, Jason D. Marshall et Robert K. Ernst. « Rationally designed TLR4 ligands for vaccine adjuvant discovery. » Journal of Immunology 198, n^o 1_Supplement (1 mai 2017) : 147.1. http://dx.doi.org/10.4049/jimmunol.198.supp.147.1.

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Abstract Adjuvant properties of bacterial cell wall components like MPLA are well described, and have gained FDA approval for use in vaccines such as Cervarix. MPLA is the product of chemically modified lipooligosaccharide (LOS), altered to diminish toxic proinflammatory effects while retaining adequate immunogenicity. Despite the virtually unlimited number of potential source bacterial strains, useable compounds within this promising class of adjuvants remain unfortunately low. We have developed bacterial enzymatic combinatorial chemistry (BECC) as a method to generate functionally diverse and rationally designed lipid A. BECC removes endogenous, or introduces exogenous, lipid A-modifying enzymes to bacteria, effectively reprogramming the lipid A biosynthetic pathway. In this study, BECC is applied within an avirulent strain of Yersinia pestis (Yp), to develop structurally distinct LOS molecules that elicit differential TLR4 activation. Using reporter cell lines that measure innate immune activated NF-κB transcription, BECC-derived molecules were screened for the ability to induce a lower pro-inflammatory response than E. coli LOS. Structures exhibit varied, dose-dependent TLR4-driven NF-κB activation with both human- and mouse-TLR4 complexes. Additional cytokine secretion screening identified molecules that induce comparable levels of TNF-α and IL-8, as compared to PHAD. Lead candidates demonstrated potent immunostimulation in mouse splenocytes, human primary PBMCs, and human monocyte-derived DC. This newly described BECC system allows for directed programming of lipid A synthesis and has the potential to generate a diverse array of TLR4 agonist candidates comparable if not preferable to PHAD and MPLA.

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Gingerich, Aaron D., Fredejah Royer, Anna L. McCormick, Anna Scasny, Jorge E. Vidal et Jarrod J. Mousa. « Synergistic Protection against Secondary Pneumococcal Infection by Human Monoclonal Antibodies Targeting Distinct Epitopes ». Journal of Immunology 210, n^o 1 (1 janvier 2023) : 50–60. http://dx.doi.org/10.4049/jimmunol.2200349.

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Abstract Streptococcus pneumoniae persists as a leading cause of bacterial pneumonia despite the widespread use of polysaccharide-based vaccines. The limited serotype coverage of current vaccines has led to increased incidence of nonvaccine serotypes, as well as an increase in antibiotic resistance among these serotypes. Pneumococcal infection often follows a primary viral infection such as influenza virus, which hinders host defense and results in bacterial spread to the lungs. We previously isolated human monoclonal Abs (mAbs) against the conserved surface Ag pneumococcal histidine triad protein D (PhtD), and we demonstrated that mAbs to this Ag are protective against lethal pneumococcal challenge prophylactically and therapeutically. In this study, we elucidated the mechanism of protection of a protective anti-pneumococcal human mAb, PhtD3, which is mediated by the presence of complement and macrophages in a mouse model of pneumococcal infection. Treatment with mAb PhtD3 reduced blood and lung bacterial burden in mice, and mAb PhtD3 is able to bind to bacteria in the presence of the capsular polysaccharide, indicating exposure of surface PhtD on encapsulated bacteria. In a mouse model of secondary pneumococcal infection, protection mediated by mAb PhtD3 and another mAb targeting a different epitope, PhtD7, was reduced; however, robust protection was restored by combining mAb PhtD3 with mAb PhtD7, indicating a synergistic effect. Overall, these studies provide new insights into anti-pneumococcal mAb protection and demonstrate, to our knowledge, for the first time, that mAbs to pneumococcal surface proteins can protect against secondary pneumococcal infection in the mouse model.

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Stephen, Donna L. « A Discussion of Avery Weisman's Notion of Appropriate Death ». OMEGA - Journal of Death and Dying 24, n^o 4 (juin 1992) : 301–8. http://dx.doi.org/10.2190/8c1x-phtd-45ed-kykx.

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This article traces uses of the term “appropriate death,” as introduced by Avery Weisman in 1970, and some of the term's philosophic difficulties. It is concluded that “appropriate death” has been used to refer to a clustering of three components: 1) consistency in functioning; 2) idiosyncratic views of appropriate; and 3) features which contribute toward a better death. It is then argued that the core concept-the one which gives the term special usefulness-is an emphasis on the idiosyncratic. Comments concerning theoretical implications of “appropriate dying” are discussed relative to the concepts of living will and euthanasia.

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Presto, Charles T. Lo, Martin F. Sherman et Margaret A. Dicarlo. « Factors Affecting the Unacceptability of Suicide and the Effects of Evaluator Depression and Religiosity ». OMEGA - Journal of Death and Dying 30, n^o 3 (1 janvier 1995) : 205–21. http://dx.doi.org/10.2190/xhth-dh29-phtd-4wvm.

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This study represents a partial replication and extension of Deluty's investigations of the factors affecting suicide unacceptability [1]. Two hundred eighty-two Catholic college students evaluated scenarios which manipulated precipitating illness (i.e., severe depression, chronic physical pain, and terminal bone cancer) and gender of victim. In addition, evaluator variables (i.e., gender, mood state, and religiosity) were also considered. Results indicated that the unacceptability of suicide is a function of precipitating illness and gender of victim as well as a function of an evaluator's mood state, and religiosity. In addition, complex interactions among several of these variables were found, suggesting the complexity of decisions regarding the unacceptability of suicide.

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André, Greiciely O., Mayara T. Borges, Lucas Assoni, Lucio F. C. Ferraz, Piplani Sakshi, Penelope Adamson, David L. Gordon et al. « Protective role of PhtD and its amino and carboxyl fragments against pneumococcal sepsis ». Vaccine 39, n^o 27 (juin 2021) : 3626–32. http://dx.doi.org/10.1016/j.vaccine.2021.04.068.

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Tassone, Joseph P., Emma V. England, Preston M. MacQueen, Michael J. Ferguson et Mark Stradiotto. « PhPAd-DalPhos : Ligand-Enabled, Nickel-Catalyzed Cross-Coupling of (Hetero)aryl Electrophiles with Bulky Primary Alkylamines ». Angewandte Chemie 131, n^o 8 (24 janvier 2019) : 2507–11. http://dx.doi.org/10.1002/ange.201812862.

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Tassone, Joseph P., Emma V. England, Preston M. MacQueen, Michael J. Ferguson et Mark Stradiotto. « PhPAd‐DalPhos : Ligand‐Enabled, Nickel‐Catalyzed Cross‐Coupling of (Hetero)aryl Electrophiles with Bulky Primary Alkylamines ». Angewandte Chemie International Edition 58, n^o 8 (18 février 2019) : 2485–89. http://dx.doi.org/10.1002/anie.201812862.

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Malekan, Mohammadali, Seyed Davar Siadat, Mohammadreza Aghasadeghi, Nader Shahrokhi, Sana Eybpoosh, Elnaz Afshari et Seyed fazlollah Mousavi. « Assessment of PhtD C-Terminal Immunogenicity by Opsonophagocytosis Assay (OPA) with OMVs as Adjuvants ». Vaccine Research 6, n^o 2 (1 décembre 2019) : 37–41. http://dx.doi.org/10.29252/vacres.6.2.37.

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Brookes, Roger H., Marin Ming, Kimberley Williams, Robert Hopfer, Sanjay Gurunathan, Scott Gallichan, Mei Tang et Martina M. Ochs. « Passive protection of mice againstStreptococcus pneumoniaechallenge by naturally occurring and vaccine-induced human anti-PhtD antibodies ». Human Vaccines & ; Immunotherapeutics 11, n^o 7 (27 avril 2015) : 1836–39. http://dx.doi.org/10.1080/21645515.2015.1039210.

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Khan, M. Nadeem, et Michael E. Pichichero. « Vaccine candidates PhtD and PhtE of Streptococcus pneumoniae are adhesins that elicit functional antibodies in humans ». Vaccine 30, n^o 18 (avril 2012) : 2900–2907. http://dx.doi.org/10.1016/j.vaccine.2012.02.023.

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Sharma, Parveen, Riffat Munir, Jocelyn Plouffe, Nidhi Shah, Teresa Kievit et David Levin. « Polyhydroxyalkanoate (PHA) Polymer Accumulation and pha Gene Expression in Phenazine (phz-) and Pyrrolnitrin (prn-) Defective Mutants of Pseudomonas chlororaphis PA23 ». Polymers 10, n^o 11 (27 octobre 2018) : 1203. http://dx.doi.org/10.3390/polym10111203.

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Pseudomonas chlororaphis PA23 was isolated from the rhizosphere of soybeans and identified as a biocontrol bacterium against Sclerotinia sclerotiorum, a fungal plant pathogen. This bacterium produces a number of secondary metabolites, including phenazine-1-carboxylic acid, 2-hydroxyphenazine, pyrrolnitrin (PRN), hydrogen cyanide, proteases, lipases and siderophores. It also synthesizes and accumulates polyhydroxyalkanoate (PHA) polymers as carbon and energy storage compounds under nutrient-limited conditions. Pseudomonads like P. chlororaphis metabolize glucose via the Entner-Doudoroff and Pentose Phosphate pathways, which provide precursors for phenazine production. Mutants defective in phenazine (PHZ; PA23-63), PRN (PA23-8), or both (PA23-63-1) accumulated higher concentrations of PHAs than the wild-type strain (PA23) when cultured in Ramsay’s Minimal Medium with glucose or octanoic acid as the carbon source. Expression levels of six pha genes, phaC1, phaZ, phaC2, phaD, phaF, and phaI, were compared with wild type PA23 by quantitative real time polymerase chain reaction (qPCR). The qPCR studies indicated that there was no change in levels of transcription of the PHA synthase genes phaC1 and phaC2 in the phz- (PA23-63) and phz- prn- (PA23-63-1) mutants in glucose medium. There was a significant increase in expression of phaC2 in octanoate medium. Transcription of phaD, phaF and phaI increased significantly in the phz- prn- (PA23-63-1) mutant. Mutations in regulatory genes like gacS, rpoS, and relA/spoT, which affect PHZ and PRN production, also resulted in altered gene expression. The expression of phaC1, phaC2, phaF, and phaI genes was down-regulated significantly in gacS and rpoS mutants. Thus, it appears that PHZ, PRN, and PHA production is regulated by common mechanisms. Higher PHA production in the phz- (PA23-63), prn- (PA23-8), and phz- prn- (PA23-63-1) mutants in octanoic medium could be correlated with higher expression of phaC2. Further, the greater PHA production observed in the phz- and prn- mutants was not due to increased transcription of PHA synthase genes in glucose medium, but due to more accessibility of carbon substrates and reducing power, which were otherwise used for the synthesis of PHZ and PRN.

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Lin, Sirong, Zheng Pei, Bin Zhang, Huili Ma et WanZhen Liang. « Vibronic Coupling Effect on the Vibrationally Resolved Electronic Spectra and Intersystem Crossing Rates of a TADF Emitter : 7-PhQAD ». Journal of Physical Chemistry A 126, n^o 2 (6 janvier 2022) : 239–48. http://dx.doi.org/10.1021/acs.jpca.1c08456.

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Tarazona, Natalia A., Ana M. Hernández‐Arriaga, Ryan Kniewel et M. Auxiliadora Prieto. « Phasin interactome reveals the interplay of PhaF with the polyhydroxyalkanoate transcriptional regulatory protein PhaD in Pseudomonas putida ». Environmental Microbiology 22, n^o 9 (6 août 2020) : 3922–36. http://dx.doi.org/10.1111/1462-2920.15175.

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Visan, Lucian, Nicolas Rouleau, Emilie Proust, Loïc Peyrot, Arnaud Donadieu et Martina Ochs. « Antibodies to PcpA and PhtD protect mice against Streptococcus pneumoniae by a macrophage- and complement-dependent mechanism ». Human Vaccines & ; Immunotherapeutics 14, n^o 2 (14 décembre 2017) : 489–94. http://dx.doi.org/10.1080/21645515.2017.1403698.

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Loisel, Elodie, Suneeta Chimalapati, Catherine Bougault, Anne Imberty, Benoit Gallet, Anne Marie Di Guilmi, Jeremy Brown, Thierry Vernet et Claire Durmort. « Biochemical Characterization of the Histidine Triad Protein PhtD as a Cell Surface Zinc-Binding Protein of Pneumococcus ». Biochemistry 50, n^o 17 (3 mai 2011) : 3551–58. http://dx.doi.org/10.1021/bi200012f.

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