Non-Metabolic Membrane Tubulation and Permeability Induced by Bioactive Peptides

BACKGROUND: Basic cell-penetrating peptides are potential vectors for therapeutic molecules and display antimicrobial activity. The peptide-membrane contact is the first step of the sequential processes leading to peptide internalization and cell activity. However, the molecular mechanisms involved in peptide-membrane interaction are not well understood and are frequently controversial. Herein, we compared the membrane activities of six basic peptides with different size, charge density and amphipaticity: Two cell-penetrating peptides (penetratin and R9), three amphipathic peptides and the neuromodulator substance P. METHODOLOGY/PRINCIPAL FINDINGS: Experiments of X ray diffraction, video-microscopy of giant vesicles, fluorescence spectroscopy, turbidimetry and calcein leakage from large vesicles are reported. Permeability and toxicity experiments were performed on cultured cells. The peptides showed differences in bilayer thickness perturbations, vesicles aggregation and local bending properties which form lipidic tubular structures. These structures invade the vesicle lumen in the absence of exogenous energy. CONCLUSIONS/SIGNIFICANCE: We showed that the degree of membrane permeabilization with amphipathic peptides is dependent on both peptide size and hydrophobic nature of the residues. We propose a model for peptide-induced membrane perturbations that explains the differences in peptide membrane activities and suggests the existence of a facilitated “physical endocytosis,” which represents a new pathway for peptide cellular internalization

Cognitive function and drivers of cognitive impairment in a European and a Korean cohort of people living with HIV

Although cognitive impairments are still prevalent in the current antiretroviral therapy era, limited investigations have compared the prevalence of cognitive disorder in people living with HIV (PLWH) and its determinants in different regions and ethnicities. We compared cognitive performance across six domains using comparable batteries in 134 PLWH aged ≥45 years from the COBRA study (Netherlands, UK), and 194 PLWH aged ≥18 years from the NeuroAIDS Project (South Korea). Cognitive scores were standardized and averaged to obtain domain and global T-scores. Associations with global T-scores were evaluated using multivariable regression and the ability of individual tests to detect cognitive impairment (global T-score ≤45) was assessed using the area-under-the-receiver-operating-characteristic curve (AUROC). The median (interquartile range) age of participants was 56 (51, 62) years in COBRA (88% white ethnicity, 93% male) and 45 (37, 52) years in NeuroAIDS (100% Korean ethnicity, 94% male). The rate of cognitive impairment was 18.8% and 18.0%, respectively (p = 0.86). In COBRA, Black-African ethnicity was the factor most strongly associated with cognitive function (11.1 [7.7, 14.5] lower scores vs. white ethnicity, p < 0.01), whereas in NeuroAIDS, age (0.6 [0.1, 1.3] per 10-year, p<0.01) and education (0.7 [0.5, 0.9] per year, p<0.01) were significantly associated with cognitive function with anemia showing only a weak association (−1.2 [−2.6, 0.3], p=0.12). Cognitive domains most associated with cognitive impairment were attention (AUROC = 0.86) and executive function (AUROC = 0.87) in COBRA and processing speed (AUROC = 0.80), motor function (AUROC = 0.78) and language (AUROC = 0.78) in NeuroAIDS. Two cohorts of PLWH from different geographical regions report similar rates of cognitive impairment but different risk factors and cognitive profiles of impairment

CNS Delivery Via Adsorptive Transcytosis

Adsorptive-mediated transcytosis (AMT) provides a means for brain delivery of medicines across the blood-brain barrier (BBB). The BBB is readily equipped for the AMT process: it provides both the potential for binding and uptake of cationic molecules to the luminal surface of endothelial cells, and then for exocytosis at the abluminal surface. The transcytotic pathways present at the BBB and its morphological and enzymatic properties provide the means for movement of the molecules through the endothelial cytoplasm. AMT-based drug delivery to the brain was performed using cationic proteins and cell-penetrating peptides (CPPs). Protein cationization using either synthetic or natural polyamines is discussed and some examples of diamine/polyamine modified proteins that cross BBB are described. Two main families of CPPs belonging to the Tat-derived peptides and Syn-B vectors have been extensively used in CPP vector-mediated strategies allowing delivery of a large variety of small molecules as well as proteins across cell membranes in vitro and the BBB in vivo. CPP strategy suffers from several limitations such as toxicity and immunogenicity—like the cationization strategy—as well as the instability of peptide vectors in biological media. The review concludes by stressing the need to improve the understanding of AMT mechanisms at BBB and the effectiveness of cationized proteins and CPP-vectorized proteins as neurotherapeutics

Do people living with HIV experience greater age advancement than their HIV-negative counterparts?

Objectives: Despite successful antiretroviral therapy, people living with HIV (PLWH) may show signs of premature/accentuated aging. We compared established biomarkers of aging in PLWH, appropriately chosen HIV-negative individuals, and blood donors, and explored factors associated with biological age advancement. Design: Cross-sectional analysis of 134 PLWH on suppressive antiretroviral therapy, 79 lifestyle-comparable HIV-negative controls aged 45 years or older from the Co-mor- Bidity in Relation to AIDS (COBRA) cohort, and 35 age-matched blood donors. Methods: Biological age was estimated using a validated algorithm based on 10 biomarkers. Associations between ‘age advancement’ (biological minus chronological age) and HIV status/parameters, lifestyle, cytomegalovirus (CMV), hepatitis B (HBV) and hepatitis C virus (HCV) infections were investigated using linear regression. Results: The average (95% CI) age advancement was greater in both HIV-positive [13.2 (11.6–14.9) years] and HIV-negative [5.5 (3.8–7.2) years] COBRA participants compared with blood donors [7.0 (4.1 to 9.9) years, both P’s<0.001)], but also in HIV-positive compared with HIV-negative participants (P<0.001). Chronic HBV, higher anti-CMV IgG titer and CD8þ T-cell count were each associated with increased age advancement, independently of HIV-status/group. Among HIV-positive participants, age advancement was increased by 3.5 (0.1–6.8) years among those with nadir CD4þ T-cell count less than 200 cells/ml and by 0.1 (0.06–0.2) years for each additional month of exposure to saquinavir

Stenodynerus oehlkei GUSENLEITNER

Stenodynerus oehlkeiGUSENLEITNER M a t e r i a l 1 Paratypus, Fluss Otuk, 2600m, 41.47 N, 75.45 E, 16.7.1999, Jacobs; 1 Paratypus, Alai- Tal, Kök-/ Kysyl-Suu, 39.40 N, 73.49 E, 2900m, 22.7.1999, H.-J. Jacobs leg.; 1 Holotypus, 1, 1 Paratypen, vor Suusamyr-Tal, 42.11 N, 73.00 E, 2400m, 31.7.1999, H.-J. Jacobs leg.; weitere Paratypen in Coll. J. Gusenleitner. V e r b r e i t u n g:Kirgisien.Published as part of Oehlke, J., 2012, Beitrag zur Kenntnis der Faltenwespen - Fauna von Kyrgyzstan (Hymenoptera, Vespidae & Eumenidae), pp. 595-600 in Linzer biologische Beiträge 44 (1) on page 599, DOI: 10.5281/zenodo.532819

Eumenes pomiformis

Eumenes pomiformis (FABRICIUS) M a t e r i a l:1, Tschylschkann.- Tal s. Dangi, 42.07 N, 72.48 E, 1600m, 30.7.1999, H.-J. Jacobs leg.; 2, Suursamyr - Tal, 42.12 N, 73.36 E, 2260m, 31.7.1999, H.-J. Jacobs leg.; 1, 2400m, Chrebet-Moldo-Too, S. Suula-Kurtka-Tal, N 41.38, E 075.02, 01.7.07, leg. Oehlke SNM: je über Hundert und doppelt so viele von Usbekistan bis Südeuropa. V e r b r e i t u n g:Kirgisien,südwestlichePaleartis.Published as part of Oehlke, J., 2012, Beitrag zur Kenntnis der Faltenwespen - Fauna von Kyrgyzstan (Hymenoptera, Vespidae & Eumenidae), pp. 595-600 in Linzer biologische Beiträge 44 (1) on page 598, DOI: 10.5281/zenodo.532819

Dolichovespula adulterina

Dolichovespula adulterina (BUYSSON) M a t e r i a l:1, 2400m, Chrebet-Moldo-Too, N 41.37, E 074.25; 28.6.07, leg. Oehlke. V e r b r e i t u n g: holarktisch.Published as part of Oehlke, J., 2012, Beitrag zur Kenntnis der Faltenwespen - Fauna von Kyrgyzstan (Hymenoptera, Vespidae & Eumenidae), pp. 595-600 in Linzer biologische Beiträge 44 (1) on page 595, DOI: 10.5281/zenodo.532819

Stenodynerus punctifrons

Stenodynerus punctifrons (THOMSON) M a t e r i a l:1, Fluss Otuk, 2600m, 41.47 N, 75.45 E, 16.07.1999, Jacobs. SNM: 11, 14 Mongolei und Südeuropa. V e r b r e i t u n g:Zentralasien,Südeuropa.Published as part of Oehlke, J., 2012, Beitrag zur Kenntnis der Faltenwespen - Fauna von Kyrgyzstan (Hymenoptera, Vespidae & Eumenidae), pp. 595-600 in Linzer biologische Beiträge 44 (1) on page 599, DOI: 10.5281/zenodo.532819

Vespula germanica

&lt;i&gt;Vespula germanica&lt;/i&gt; (FABRICIUS) &lt;p&gt;M a t e r i a l:1, 2400m, Chrebet-Moldo-Too S, Suula-Kurka-Tal, N 41.38, E 5.02; 01.7.07, leg. Oehlke.&lt;/p&gt; &lt;p&gt;V e r b r e i t u n g: weltweit.&lt;/p&gt;Published as part of &lt;i&gt;Oehlke, J., 2012, Beitrag zur Kenntnis der Faltenwespen - Fauna von Kyrgyzstan (Hymenoptera, Vespidae &amp; Eumenidae), pp. 595-600 in Linzer biologische Beiträge 44 (1)&lt;/i&gt; on page 596, DOI: &lt;a href="http://zenodo.org/record/5328195"&gt;10.5281/zenodo.5328195&lt;/a&gt

Beitrag zur Kenntnis der Faltenwespen - Fauna von Kyrgyzstan (Hymenoptera, Vespidae & Eumenidae)

Oehlke, J. (2012): Beitrag zur Kenntnis der Faltenwespen - Fauna von Kyrgyzstan (Hymenoptera, Vespidae & Eumenidae). Linzer biologische Beiträge 44 (1): 595-600, DOI: http://doi.org/10.5281/zenodo.532819