| 1. |
- Coleman, M., et al.
(författare)
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Hyaluronidase Impairs Neutrophil Function and Promotes Group B Streptococcus Invasion and Preterm Labor in Nonhuman Primates
- 2021
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Ingår i: Mbio. - 2150-7511. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Invasive bacterial infections during pregnancy are a major risk factor for preterm birth, stillbirth, and fetal injury. Group B streptococci (GBS) are Gram-positive bacteria that asymptomatically colonize the lower genital tract but infect the amniotic fluid and induce preterm birth or stillbirth. Experimental models that closely emulate human pregnancy are pivotal for the development of successful strategies to prevent these adverse pregnancy outcomes. Using a unique nonhuman primate model that mimics human pregnancy and informs temporal events surrounding amniotic cavity invasion and preterm labor, we show that the animals inoculated with hyaluronidase (HylB)-expressing GBS consistently exhibited microbial invasion into the amniotic cavity, fetal bacteremia, and preterm labor. Although delayed cytokine responses were observed at the maternal-fetal interface, increased prostaglandin and matrix metalloproteinase levels in these animals likely mediated pre term labor. HylB-proficient GBS dampened reactive oxygen species production and exhibited increased resistance to neutrophils compared to an isogenic mutant. Together, these findings demonstrate how a bacterial enzyme promotes GBS amniotic cavity invasion and preterm labor in a model that closely resembles human pregnancy. IMPORTANCE Group B streptococci (GBS) are bacteria that commonly reside in the female lower genital tract as asymptomatic members of the microbiota. However, during pregnancy, GBS can infect tissues at the maternal-fetal interface, leading to preterm birth, stillbirth, or fetal injury. Understanding how GBS evade host defenses during pregnancy is key to developing improved preventive therapies for these adverse outcomes. In this study, we used a unique nonhuman primate model to show that an enzyme secreted by GBS, hyaluronidase (HylB) promotes bacterial invasion into the amniotic cavity and fetus. Although delayed immune responses were seen at the maternal-fetal interface, animals infected with hyaluronidase-expressing GBS exhibited premature cervical ripening and preterm labor. These observations reveal that HylB is a crucial GBS virulence factor that promotes bacterial invasion and preterm labor in a pregnancy model that closely emulates human pregnancy. Therefore, hyaluronidase inhibitors may be useful in therapeutic strategies against ascending GBS infection.
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| 2. |
- Sultan, B Bin Mohamad, et al.
(författare)
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Selective dissolution during acid pickling of aluminum alloys by element-resolved electrochemistry
- 2022
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Ingår i: Electrochimica Acta. - : Elsevier Ltd. - 0013-4686 .- 1873-3859. ; 404
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Tidskriftsartikel (refereegranskat)abstract
- The surface reactivity and the elemental dissolution of a high-strength aerospace alloy (AA7449-T651) during acid pickling was investigated with element-resolved electrochemistry (AESEC). The results demonstrated a sequential dissolution of Mg, Al, Zn and Cu, following the order of their respective galvanic reactivity in common acid pickling solutions. The enrichment of Cu during pickling with the H2SO4 solution was observed. The effect of oxidizing solution components HNO3 and Fe(III) on Cu dissolution were investigated using an experimental Evans diagram approach.
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| 3. |
- Sultan, BBM, et al.
(författare)
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On the dissolution rates and mechanisms of Al-Mg and Al-Cu alloys during acid pickling using element-resolved electrochemistry
- 2023
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Ingår i: Electrochimica Acta. - : Elsevier Ltd. - 0013-4686 .- 1873-3859. ; 444
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Tidskriftsartikel (refereegranskat)abstract
- Acid pickling is a one-step process prior to the conversion coating of aluminum alloys, an alternative to the two-step degreasing-deoxidizing. Selective dissolution may lead to enrichment or depletion of alloying elements with important consequences for corrosion resistance. In this work, the mechanisms of selective dissolution were explored using element-resolved electrochemistry for Al-3at.%Cu and Al-3at.%Mg, representing two extremes of the galvanic series. Pickling reactions were investigated in sulfuric and nitric acids with and without Fe(III) additives. The microstructure of the Al-3at.%Cu alloy was varied by heat treatment. Al-3at.%Mg showed congruent dissolution throughout the steady state in all electrolytes while Al-3at.%Cu underwent selective dissolution with surface enrichment of Cu and a significant release of detached Cu-rich particles in sulfuric acid. With the presence of Fe(III) in the electrolyte, Cu dissolved congruently, and the dissolution kinetics of these two alloys were also markedly enhanced. Experimental Evans diagrams were determined to clarify the electrochemical nature of the reactions. © 2023 The Author(s)
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| 4. |
- Wetten, Aaron, et al.
(författare)
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Neurosteroid activation of gaba-a receptors : a potential treatment target for symptoms in primary biliary cholangitis?
- 2022
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Ingår i: Canadian journal of gastroenterology & hepatology. - : Hindawi Publishing Corporation. - 2291-2789 .- 2291-2797. ; 2022
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: A third of patients with primary biliary cholangitis (PBC) experience poorly understood cognitive symptoms, with a significant impact on quality of life (QOL), and no effective medical treatment. Allopregnanolone, a neurosteroid, is a positive allosteric modulator of gamma-aminobutyricacid-A (GABA-A) receptors, associated with disordered mood, cognition, and memory. This study explored associations between allopregnanolone and a disease-specific QOL scoring system (PBC-40) in PBC patients.Method: Serum allopregnanolone levels were measured in 120 phenotyped PBC patients and 40 age and gender-matched healthy controls. PBC subjects completed the PBC-40 at recruitment. Serum allopregnanolone levels were compared across PBC-40 domains for those with none/mild symptoms versus severe symptoms.Results: There were no overall differences in allopregnanolone levels between healthy controls (median = 0.03 ng/ml (IQR = 0.025)) and PBC patients (0.031 (0.42), p = 0.42). Within the PBC cohort, higher allopregnanolone levels were observed in younger patients (r (120) = -0.53, p < 0.001) but not healthy controls (r (39) = -0.21, p = 0.21). Allopregnanolone levels were elevated in the PBC-40 domains, cognition (u = 1034, p = 0.02), emotional (u = 1374, p = 0.004), and itch (u = 795, p = 0.03). Severe cognitive symptoms associated with a younger age: severe (50 (12)) vs. none (60 (13); u = 423 p = 0.001).Conclusion: Elevated serum allopregnanolone is associated with severe cognitive, emotional, and itch symptoms in PBC, in keeping with its known action on GABA-A receptors. Existing novel compounds targeting allopregnanolone could offer new therapies in severely symptomatic PBC, satisfying a significant unmet need.
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