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  1. Article ; Online: A duplex structure of SARM1 octamers stabilized by a new inhibitor [Correction: Mar. 2023, 80(3), p. 68]

    Khazma, Tami / Golan-Vaishenker, Yarden / Guez-Haddad, Julia / Grossman, Atira / Sain, Radhika / Weitman, Michal / Plotnikov, Alexander / Zalk, Ran / Yaron-Kritzmar, Abraham / Hons, Michael / Opatowsky, Yarden

    Cell. Mol. Life Sci.. 2023 Jan., v. 80, no. 1, p. 16

    2023  , Page(s) 16

    Abstract: In recent years, there has been growing interest in SARM1 as a potential breakthrough drug target for treating various pathologies of axon degeneration. SARM1-mediated axon degeneration relies on its TIR domain NADase activity, but recent structural data ...

    Abstract In recent years, there has been growing interest in SARM1 as a potential breakthrough drug target for treating various pathologies of axon degeneration. SARM1-mediated axon degeneration relies on its TIR domain NADase activity, but recent structural data suggest that the non-catalytic ARM domain could also serve as a pharmacological site as it has an allosteric inhibitory function. Here, we screened for synthetic small molecules that inhibit SARM1, and tested a selected set of these compounds in a DRG axon degeneration assay. Using cryo-EM, we found that one of the newly discovered inhibitors, a calmidazolium designated TK106, not only stabilizes the previously reported inhibited conformation of the octamer, but also a meta-stable structure: a duplex of octamers (16 protomers), which we have now determined to 4.0 Å resolution. In the duplex, each ARM domain protomer is engaged in lateral interactions with neighboring protomers, and is further stabilized by contralateral contacts with the opposing octamer ring. Mutagenesis of the duplex contact sites leads to a moderate increase in SARM1 activation in cultured cells. Based on our data we propose that the duplex assembly constitutes an additional auto-inhibition mechanism that tightly prevents pre-mature activation and axon degeneration.
    Keywords axons ; drugs ; mutagenesis ; protein subunits
    Language English
    Dates of publication 2023-01
    Size p. 16
    Publishing place Springer International Publishing
    Document type Article ; Online
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-022-04641-3
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 4' 47/14: Show issues

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  2. Article ; Online: Molecular detection of feline hemoplasmas and retroviruses in free-roaming and shelter cats within a university campus [Mar. 2023, 9(1), p. 20551169231162671]

    Yamakawa, Ana Carolina / Haisi, Amanda / Kmetiuk, Louise Bach / Pellizzaro, Maysa / Mendes, Juliana Cristina Rebonato / Canavessi, Aurea Maria Oliveira / Ullmann, Leila Sabrina / de Castro, Wagner Antônio Chiba / Pessoa Araújo Júnior, João / Santos, Andrea Pires dos / Biondo, Alexander Welker

    Journal of Feline Medicine and Surgery Open Reports. 2023 Feb., v. 9, no. 1, p. 20551169221148672

    2023  , Page(s) 20551169221148672

    Abstract: ... significantly lower packed cell volumes (P = 0.037). Although 5/23 (21.7%) males and 1/22 (4.6%) females were ... positive, no statistically significant association between sex and hemoplasma infection was found (P = 0.19 ... for FIV and none for FeLV. Only one cat (2.3%) was coinfected with hemoplasma and FIV (P = 0.26 ...

    Abstract The aim of the present study was to assess the frequency of hemoplasma, feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) infections in cats living in an on-campus shelter and free-roaming cats within a university campus in Brazil. Blood samples were tested using quantitative PCR for hemoplasma, FIV and FeLV. Positive hemoplasma samples were sequenced. Associations between hemoplasma detection and living situation, sex, flea and/or tick parasitism, and coinfection with FIV and FeLV, were assessed using Fisher’s exact test and the respective odds ratios were calculated. Overall, 6/45 (13.3%) cats tested positive: four (8.9%) were infected with ‘Candidatus Mycoplasma haemominutum’ and two (4.4%) with Mycoplasma haemofelis. All positive samples were from free-roaming cats (6/15; 40.0%) and had statistically significantly lower packed cell volumes (P = 0.037). Although 5/23 (21.7%) males and 1/22 (4.6%) females were positive, no statistically significant association between sex and hemoplasma infection was found (P = 0.19). Viral quantitative PCR (qPCR) was performed on 43/45 samples, among which 2/43 (4.7%) were positive for FIV and none for FeLV. Only one cat (2.3%) was coinfected with hemoplasma and FIV (P = 0.26). In addition, 4/6 (66.7%) cats that tested positive for hemoplasmas were infested by fleas (P = 0.0014) and/or ticks (P = 0.25). These results show that even if the free-roaming cat population is clinically healthy and has adequate access to food, it may present flea infestation and hemoplasma infection with lower packed cell volume values.
    Keywords Feline immunodeficiency virus ; Feline leukemia virus ; Mycoplasma haemofelis ; Mycoplasma haemominutum ; Siphonaptera ; blood ; cats ; hematocrit ; medicine ; mixed infection ; parasitism ; quantitative polymerase chain reaction ; surgery ; ticks ; Brazil ; Animal health ; coinfection ; hemotropic mycoplasma ; molecular diagnosis
    Language English
    Dates of publication 2023-02
    Size p. 20551169221148672
    Publishing place SAGE Publications
    Document type Article ; Online
    ZDB-ID 2822177-1
    ISSN 2055-1169
    ISSN 2055-1169
    DOI 10.1177/20551169221148672
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  3. Article ; Online: Discovery of candidate HIV-1 latency biomarkers using an OMICs approach [Corrigendum: Mar. 2023, v. 580, p. 61]

    Belshan, Michael / Holbrook, Alexander / George, Joseph W. / Durant, Hannah E. / Callahan, Michael / Jaquet, Spencer / West, John T. / Siedlik, Jacob / Ciborowski, Paweł

    Virology. 2021 June, v. 558, p. 86-95

    2021  , Page(s) 86–95

    Abstract: Infection with HIV-1 remains uncurable due to reservoirs of latently infected cells. Any potential cure for HIV will require a mechanism to identify and target these cells in vivo. We created a panel of Jurkat cell lines latently infected with the HIV ... ...

    Abstract Infection with HIV-1 remains uncurable due to reservoirs of latently infected cells. Any potential cure for HIV will require a mechanism to identify and target these cells in vivo. We created a panel of Jurkat cell lines latently infected with the HIV DuoFlo virus to identify candidate biomarkers of latency. SWATH mass spectrometry was used to compare the membrane proteomes of one of the cell lines to parental Jurkat cells. Several candidate proteins with significantly altered expression were identified. The differential expression of several candidates was validated in multiple latently infected cell lines. Three factors (LAG-3, CD147,CD231) were altered across numerous cell lines, but the expression of most candidate biomarkers was variable. These results confirm that phenotypic differences in latently infected cells exists and identify additional novel biomarkers. The variable expression of biomarkers across different cell clones suggests universal antigen-based detection of latently infected cells may require a multiplex approach.
    Keywords biomarkers ; gene expression regulation ; mass spectrometry ; phenotype ; proteome ; virology ; viruses ; HIV ; Latency ; SWATH-MS ; Proteomics ; Biomarker discovery
    Language English
    Dates of publication 2021-06
    Size p. 86-95
    Publishing place Elsevier Inc.
    Document type Article ; Online
    Note Resource is Open Access
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2021.03.003
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 3686: Show issues

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  4. Article ; Online: Acute Interstitial Nephritis on Positron-Emission Tomography-Computed Tomography Imaging.

    Miao, Jing / Alexander, Mariam P / Zoghby, Ziad M

    Kidney medicine

    2022  Volume 4, Issue 11, Page(s) 100552

    Language English
    Publishing date 2022-09-30
    Publishing country United States
    Document type Editorial
    ISSN 2590-0595
    ISSN (online) 2590-0595
    DOI 10.1016/j.xkme.2022.100552
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  5. Article ; Online: Highly Sensitized Candidates Remain at Risk for Microvascular Inflammation Even When Donor-specific Antibody Is Avoided: A Matched Cohort Study.

    Agrawal, Amogh / Balakrishnan, Suryanarayanan / Gandhi, Manish J / Alexander, Mariam P / Cornell, Lynn / Bentall, Andrew J / Kukla, Aleksandra / Stegall, Mark / Schinstock, Carrie A

    Transplantation

    2024  

    Abstract: ... 17/49) versus 12% (6/49), P = 0.0003] over a median (interquartile range) follow-up of 5 (4-6) y ...

    Abstract Background: Microvascular inflammation (MVI) is a key feature of antibody-mediated rejection (AMR) among patients with HLA donor-specific antibody (DSA), but MVI at AMR thresholds (Banff glomerulitis [g] + peritubular capillaritis [ptc] score ≥ 2) without DSA has been increasingly recognized. We aimed to determine the incidence of MVI among highly sensitized kidney transplant recipients without DSA.
    Methods: We performed a single-center, retrospective, matched cohort study comparing outcomes of kidney transplant recipients with cPRA ≥90% with preexisting DSA (n = 49), cPRA ≥90% without preexisting DSA (n = 47), and matched controls with cPRA = 0 without preexisting DSA (n = 49). Controls were matched by age, donor type, and transplant date. Indication and surveillance biopsies combined with annual de novo DSA screening were obtained.
    Results: Kidney transplant recipients with a cPRA ≥90% and no evidence of preexisting or de novo DSA had a higher incidence of MVI (glomerulitis + peritubular capillaritis ≥ 2) than patients with cPRA = 0 [35% (17/49) versus 12% (6/49), P = 0.0003] over a median (interquartile range) follow-up of 5 (4-6) y posttransplant. Among this cPRA ≥90% group without DSA, MVI persisted in 54% of cases on follow-up biopsy (7/13), and 24% (4/13) of cases developed transplant glomerulopathy (Banff cg score > 0).
    Conclusions: Highly sensitized transplant recipients have a high incidence of persistent and progressive MVI, even without DSA. The mechanisms underlying these histologic features needs to be elucidated, but this information is important to consider when making decisions about transplantation among highly sensitized individuals.
    Language English
    Publishing date 2024-04-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/TP.0000000000005011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 488: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 509: Show issues

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  6. Article ; Online: Smoldering giant cell arteritis in a coronary artery.

    Kaymakci, Mahmut / Elfishawi, Mohanad / Alexander, Mariam P / Koster, Matthew J / Warrington, Kenneth J

    Rheumatology (Oxford, England)

    2022  Volume 61, Issue 12, Page(s) e384–e385

    MeSH term(s) Humans ; Giant Cell Arteritis/complications ; Giant Cell Arteritis/diagnosis ; Coronary Vessels ; Temporal Arteries ; Diagnosis, Differential
    Language English
    Publishing date 2022-06-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/keac321
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    In stock of ZB MED Cologne/Königswinter

    Zs.B 240: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 497: Show issues

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  7. Article ; Online: Heavy Chain/Light Chain Antibody Immunofluorescence to Identify Monoclonal Plasma Cells in a Case of Plasma Cell-Rich Acute Interstitial Nephritis.

    Yarandi, Niloufarsadat / Alexander, Mariam P / Nasr, Samih H / Leung, Nelson

    Kidney medicine

    2022  Volume 4, Issue 8, Page(s) 100514

    Abstract: Heavy/light chain (HLC) antibodies can be used to quantify intact HLC pairs. In immunofluorescence studies, they allow differentiation of monoclonal versus polyclonal immunoglobulin deposits in kidney diseases that occur in the setting of monoclonal ... ...

    Abstract Heavy/light chain (HLC) antibodies can be used to quantify intact HLC pairs. In immunofluorescence studies, they allow differentiation of monoclonal versus polyclonal immunoglobulin deposits in kidney diseases that occur in the setting of monoclonal gammopathy. Here, we present a case of a patient with acute kidney injury with first kidney biopsy suggestive of acute interstitial nephritis with a polymorphous infiltrate of plasma cells. Routine immunofluorescence did not show a monotypic plasma cell infiltrate. Serum protein electrophoresis and immunofixation revealed monoclonal immunoglobulin A (IgA) lambda. She improved with steroid therapy, but kidney function worsened after steroids were stopped. She underwent a second kidney biopsy, which showed plasma cell-rich interstitial infiltrate with a population of IgA lambda-restricted plasma cells on routine immunofluorescence. In light of this finding, Hevylite HLC antibody was used to reassess the first biopsy, which confirmed the presence of a population of plasma cells with IgA lambda restriction. Because of the presence of monotypic plasma cells, anti-CD38 monoclonal antibody (daratumumab) was initiated.
    Language English
    Publishing date 2022-06-28
    Publishing country United States
    Document type Case Reports
    ISSN 2590-0595
    ISSN (online) 2590-0595
    DOI 10.1016/j.xkme.2022.100514
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  8. Article ; Online: Clinicopathologic Findings in Mass Forming ANCA-Associated Vasculitis.

    Gilani, Sarwat I / Alexander, Mariam P / Nasr, Samih H / Fidler, Mary E / Takahashi, Naoki / Cornell, Lynn D

    Kidney international reports

    2022  Volume 7, Issue 12, Page(s) 2709–2713

    Language English
    Publishing date 2022-09-29
    Publishing country United States
    Document type Journal Article
    ISSN 2468-0249
    ISSN (online) 2468-0249
    DOI 10.1016/j.ekir.2022.09.019
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  9. Article: Recurrent Glomerulonephritis in the Kidney Allograft.

    Bobart, Shane A / Alexander, Mariam P / Bentall, Andrew

    Indian journal of nephrology

    2020  Volume 30, Issue 6, Page(s) 359–369

    Abstract: Renal transplantation is the preferred form of renal replacement therapy in patients who develop end-stage kidney disease (ESKD). Among the diverse etiologies of ESKD, glomerulonephritis is the third most common cause, behind hypertensive and diabetic ... ...

    Abstract Renal transplantation is the preferred form of renal replacement therapy in patients who develop end-stage kidney disease (ESKD). Among the diverse etiologies of ESKD, glomerulonephritis is the third most common cause, behind hypertensive and diabetic kidney disease. Although efforts to prolong graft survival have improved over time with the advent of novel immunosuppression, recurrent glomerulonephritis remains a major threat to renal allograft survival despite concomitant immunosuppression. As a result, clinical expertise, early diagnosis and intervention will help identify recurrent disease and facilitate prompt treatment, thus minimizing graft loss, resulting in improved outcomes. In this review, we highlight the clinicopathologcal characteristics of certain glomerular diseases that recur in the renal allograft.
    Language English
    Publishing date 2020-11-30
    Publishing country India
    Document type Journal Article ; Review
    ZDB-ID 2134388-3
    ISSN 1998-3662 ; 0971-4065
    ISSN (online) 1998-3662
    ISSN 0971-4065
    DOI 10.4103/ijn.IJN_193_19
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  10. Article ; Online: Early Warning for the Electrolyzer: Monitoring CO

    Warkentin, Hugh / O'Brien, Colin P / Holowka, Sarah / Maxwell, Benjamin / Awara, Mariam / Bouman, Mark / Zeraati, Ali Shayesteh / Nicholas, Rachael / Ip, Alexander H / Elsahwi, Essam S / Gabardo, Christine M / Sinton, David

    ChemSusChem

    2023  Volume 16, Issue 23, Page(s) e202300657

    Abstract: The electrochemical ... ...

    Abstract The electrochemical CO
    Language English
    Publishing date 2023-08-25
    Publishing country Germany
    Document type Journal Article
    ISSN 1864-564X
    ISSN (online) 1864-564X
    DOI 10.1002/cssc.202300657
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