Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell penetrating peptides

Recent molecular dynamics simulations (Herce and Garcia, PNAS, 104: 20805 (2007)) have suggested that the arginine-rich HIV Tat peptides might be able to translocate by destabilizing and inducing transient pores in phospholipid bilayers. In this pathway for peptide translocation, arginine residues play a fundamental role not only in the binding of the peptide to the surface of the membrane but also in the destabilization and nucleation of transient pores across the bilayer, despite being charged and highly hydrophilic. Here we present a molecular dynamics simulation of a peptide composed of nine arginines (Arg-9) that shows that this peptide follows the same translocation pathway previously found for the Tat peptide. We test this hypothesis experimentally by measuring ionic currents across phospholipid bilayers and cell membranes through the pores induced by Arg-9 peptides. We find that Arg-9 peptides, in the presence of an electrostatic potential gradient, induce ionic currents across planar phospholipid bilayers, as well as in cultured osteosarcoma cells and human smooth muscle cells freshly isolated from the umbilical artery. Our results suggest that the mechanism of action of Arg-9 peptide involves the creation of transient pores in lipid bilayers and cell membranes.Comment: This is an extended version of the published manuscript, which had to be shortened before publication to fit within the number of pages required by the journa

Superefficient microcombs at the wafer level

Photonic integrated circuits utilize planar waveguides to process light on a chip, encompassing functions like generation, routing, modulation, and detection. Similar to the advancements in the electronics industry, photonics research is steadily transferring an expanding repertoire of functionalities onto integrated platforms. The combination of best-in-class materials at the wafer-level increases versatility and performance, suitable for large-scale markets, such as datacentre interconnects, lidar for autonomous driving or consumer health. These applications require mature integration platforms to sustain the production of millions of devices per year and provide efficient solutions in terms of power consumption and wavelength multiplicity for scalability. Chip-scale frequency combs offer massive wavelength parallelization, holding a transformative potential in photonic system integration, but efficient solutions have only been reported at the die level. Here, we demonstrate a silicon nitride technology on a 100 mm wafer that aids the performance requirements of soliton microcombs in terms of yield, spectral stability, and power efficiency. Soliton microcombs are reported with an average conversion efficiency exceeding 50%, featuring 100 lines at 100 GHz repetition rate. We further illustrate the enabling possibilities of the space multiplicity, i.e., the large wafer-level redundancy, for establishing new sensing applications, and show tri-comb interferometry for broadband phase-sensitive spectroscopy. Combined with heterogeneous integration of lasers, we envision a proliferation of high-performance photonic systems for applications in future navigation systems, data centre interconnects, and ranging

Massive Clumps in the NGC 6334 Star Forming Region

We report observations of dust continuum emission at 1.2 mm toward the star forming region NGC 6334 made with the SEST SIMBA bolometer array. The observations cover an area of $\sim 2$ square degrees with approximately uniform noise. We detected 181 clumps spanning almost three orders of magnitude in mass (3\Msun$-6\times10^3$ \Msun) and with sizes in the range 0.1--1.0 pc. We find that the clump mass function $dN/d\log M$ is well fit with a power law of the mass with exponent -0.6 (or equivalently $dN/dM \propto M^{-1.6}$). The derived exponent is similar to those obtained from molecular line emission surveys and is significantly different from that of the stellar initial mass function. We investigated changes in the mass spectrum by changing the assumptions on the temperature distribution of the clumps and on the contribution of free-free emission to the 1.2 mm emission, and found little changes on the exponent. The Cumulative Mass Distribution Function is also analyzed giving consistent results in a mass range excluding the high-mass end where a power-law fit is no longer valid. The masses and sizes of the clumps observed in NGC 6334 indicate that they are not direct progenitors of stars and that the process of fragmentation determines the distribution of masses later on or occurs at smaller spatial scales. The spatial distribution of the clumps in NGC 6334 reveals clustering which is strikingly similar to that exhibited by young stars in other star forming regions. A power law fit to the surface density of companions gives $\Sigma\propto \theta^{-0.62}$.Comment: 16 pages, 11 figures, 4 tables. To appear in the Astrophysical Journa

Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides

Recent molecular-dynamics simulations have suggested that the arginine-rich HIV Tat peptides translocate by destabilizing and inducing transient pores in phospholipid bilayers. In this pathway for peptide translocation, Arg residues play a fundamental role not only in the binding of the peptide to the surface of the membrane, but also in the destabilization and nucleation of transient pores across the bilayer. Here we present a molecular-dynamics simulation of a peptide composed of nine Args (Arg-9) that shows that this peptide follows the same translocation pathway previously found for the Tat peptide. We test experimentally the hypothesis that transient pores open by measuring ionic currents across phospholipid bilayers and cell membranes through the pores induced by Arg-9 peptides. We find that Arg-9 peptides, in the presence of an electrostatic potential gradient, induce ionic currents across planar phospholipid bilayers, as well as in cultured osteosarcoma cells and human smooth muscle cells. Our results suggest that the mechanism of action of Arg-9 peptides involves the creation of transient pores in lipid bilayers and cell membranes.Facultad de Ciencias Exacta

Probing ISM Structure in Trumpler 14 & Carina I Using The Stratospheric Terahertz Observatory 2

We present observations of the Trumpler 14/Carina I region carried out using the Stratospheric Terahertz Observatory 2 (STO2). The Trumpler 14/Carina I region is in the west part of the Carina Nebula Complex, which is one of the most extreme star-forming regions in the Milky Way. We observed Trumpler 14/Carina I in the 158 $\mu$m transition of [C\,{\sc ii}] with a spatial resolution of 48$''$ and a velocity resolution of 0.17 km s$^{-1}$. The observations cover a 0.25$^\circ$ by 0.28$^\circ$ area with central position {\it l} = 297.34$^\circ$, {\it b} = -0.60$^\circ$. The kinematics show that bright [C\,{\sc ii}] structures are spatially and spectrally correlated with the surfaces of CO clouds, tracing the photodissociation region and ionization front of each molecular cloud. Along 7 lines of sight that traverse Tr 14 into the dark ridge to the southwest, we find that the [C\,{\sc ii}] luminosity from the HII region is 3.7 times that from the PDR. In same los we find in the PDRs an average ratio of 1:4.1:5.6 for the mass in atomic gas:dark-CO gas: molecular gas traced by CO. Comparing multiple gas tracers including HI 21cm, [C\,{\sc ii}], CO, and radio recombination lines, we find that the HII regions of the Carina Nebula Complex are well-described as HII regions with one-side freely expanding towards us, consistent with the champagne model of ionized gas evolution. The dispersal of the GMC in this region is dominated by EUV photoevaporation; the dispersal timescale is 20-30 Myr.Comment: ApJ accepte

Visibilidad de los sanitarios durante la crisis del Covid-19: estudio de fuentes y temáticas en los informativos de televisión

Esta investigación analiza la cobertura mediática de la crisis del Covid-19 en España, y el papel que en ella ha tenido la comunicación sobre salud y sobre los profesionales sanitarios. Se estudia el tratamiento recibido por las fuentes y temas sanitarios en los informativos de Radiotelevisión Española (RTVE) emitidos entre el 31 diciembre 2019 y el 8 junio 2020. Para ello, se realiza un análisis de contenido cuantitativo de 452 noticias de 21 informativos. Los resultados muestran que los debates de política y los propios políticos ocupan más espacio como tema y fuentes, respectivamente, en los informativos analizados, por delante de la salud y de los profesionales sanitarios. El estudio confirma, por tanto, la falta de visibilidad de los profesionales de salud en la cobertura informativa televisiva en España sobre el Covid-19

Displaced Voices: A Journal of Migration, Archives and Cultural Heritage, Volume 3 Issue 2 (Autumn 2023)

Twentieth Century Histories of Civic Society’s Responses to Crises of Displacement: A Special Issue to mark the 70th Anniversary of Refugee Council Displaced Voices is a biannual digital magazine produced twice a year by the Living Refugee Archive team at the University of East London. Displaced Voices aims to provide a digital platform for activists, archivists, researchers, practitioners and academics to contribute to issues pertaining to refugee and migration history; refugee and migrant rights; social justice; cultural heritage and archives. We welcome a range of contributions to the magazine including articles of between 1000-2000 words; reports on fieldwork in archival collections; book recommendations and reviews; and more creative pieces including (but not limited too) cartoons; photography; and poetry. We would also welcome news on activities; publication of reports, projects; letters and news from your own networks. We welcome submissions from all writers whether you are a student, practitioner, activist or established academic. The Displaced Voices online magazine is born out of the collaborative and intersectional work that we have been undertaking through our work with the refugee and migration archives housed at the University of East London. Our work to date has explored the intersections of refugee and migration studies with narrative and life history research linked to oral history methods and archival approaches to the preservation, documentation and accessibility of archival resources recording the refugee experience. This magazine is a collaborative project between the Living Refugee Archive at the University of East London; the Oral History Society Migration Special Interest Group and the International Association for the Study of Forced Migration Working Group on the History of Forced Migration and Refugees. Thematically we are looking to engage with articles that explore the intersection of refugee and forced migration studies; history and cultural heritage studies; narrative research; oral history and archival science

Organ-specific responses during brain death:increased aerobic metabolism in the liver and anaerobic metabolism with decreased perfusion in the kidneys

Hepatic and renal energy status prior to transplantation correlates with graft survival. However, effects of brain death (BD) on organ-specific energy status are largely unknown. We studied metabolism, perfusion, oxygen consumption, and mitochondrial function in the liver and kidneys following BD. BD was induced in mechanically-ventilated rats, inflating an epidurally-placed Fogarty-catheter, with sham-operated rats as controls. A 9.4T-preclinical MRI system measured hourly oxygen availability (BOLD-related R2*) and perfusion (T1-weighted). After 4 hrs, tissue was collected, mitochondria isolated and assessed with high-resolution respirometry. Quantitative proteomics, qPCR, and biochemistry was performed on stored tissue/plasma. Following BD, the liver increased glycolytic gene expression (Pfk-1) with decreased glycogen stores, while the kidneys increased anaerobic- (Ldha) and decreased gluconeogenic-related gene expression (Pck-1). Hepatic oxygen consumption increased, while renal perfusion decreased. ATP levels dropped in both organs while mitochondrial respiration and complex I/ATP synthase activity were unaffected. In conclusion, the liver responds to increased metabolic demands during BD, enhancing aerobic metabolism with functional mitochondria. The kidneys shift towards anaerobic energy production while renal perfusion decreases. Our findings highlight the need for an organ-specific approach to assess and optimise graft quality prior to transplantation, to optimise hepatic metabolic conditions and improve renal perfusion while supporting cellular detoxification