The acylhalocapnines of halophilic bacteria: structural details of unusual sulfonate sphingoids

Sulfonate sphingoids or sulfonolipids are bioactive unusual compounds found in members of the Bacteroidetes family. The present report describes the structures of sulfonolipids of halophilic bacteria, sharing structural similarity with compounds of fungal origin inhibiting the serine palmitoyl transferase and with capnines, known as antagonists of von Willebrandt factor. Two sulfonolipids (SL1 and SL2) were isolated from the lipid extract of the halophile Salisaeta longa and analyzed by ESI-MS/MS. SL1 and SL2 structures have in common the long chain aminosulfonate 2-carboxy-2-amino-3,4-hydroxy-17 methyloctadec-5-ene-1-sulfonic for which the common name of halocapnine is suggested. The hydroxyl group on carbon 3 of aminosulfonate moiety is acylated: iso C15 and iso hydroxy C15 chains are present in SL1 and SL2, respectively. The levels of the two different sulfonolipids in the bacterium were found to be modulated by the proportion of sodium and magnesium ions in the environment.     

Manganese superoxide dismutase inactivation during Fas (CD95)-mediated apoptosis in Jurkat T cells

Manganese superoxide dismutase (MnSOD, SOD2) is an essential primary antioxidant enzyme which converts superoxide radical to hydrogen peroxide within the mitochondrial matrix. MnSOD plays a prominent role in protection against many apoptotic stimuli. Its absence may therefore impair the cellular redox balance and enhance apoptosis. Our data show that in Jurkat T cells, following oligomerization of the Fas receptor, MnSOD is selectively degraded during apoptosis. In the presence of cycloheximide, an inhibitor of protein synthesis, the rates of cell death and MnSOD degradation were accelerated. Fas-induced MnSOD cleavage was partially inhibited in the presence of the pan-caspase inhibitor, z-VAD-fmk. MnSOD in the mitochondrial fractions was cleaved in vitro by treatment with the cytosolic fraction of Fas-activated cells. Moreover, two possible cleavage sites of recombinant hMnSOD by direct interaction with recombinant caspase-3 were noted. Cellular and mitochondrial factors were found to be necessary for the interaction. These factors include intracellular mobilization of calcium. Our data indicate that inactivation of MnSOD in receptor-mediated apoptosis by caspase-specific degradation would render the mitochondria sensitive to the steady-state production of superoxide, decrease the steady-state flux of H₂O₂, expedite the loss of mitochondrial function, and potentiate apoptosis.     

Archaeological horizons and fluvial processes at the Lower Paleolithic open-air site of Revadim (Israel)

In this paper we present new data pertaining to the paleo-landscape characteristics at the Acheulian site of Revadim, on the southern coastal plain of Israel. Sedimentological, isotopic, granulometric and micromorphological studies showed that the archaeological remains accumulated in an active fluvial environment where channel action, overbank flooding and episodic inundation occurred. Measurements of total organic matter and its carbon isotopic composition indicate that the hominin activity at the site started at a period of relatively drier conditions, which coincided with erosion of the preceding soil sequence. This process led to the formation of a gently-undulating topography, as reconstructed by a GIS model. Later deposition documents relatively wetter conditions, as indicated by carbon isotopic composition. Formation processes identified at the site include fluvial processes, inundation episodes that resulted in anaerobic conditions and formation of oxide nodules, as well as small-scale bioturbation and later infiltration of carbonate-rich solutions that resulted in the formation of calcite nodules and crusts. The combination of micro-habitats created favorable conditions that repeatedly drew hominins to the area, as seen by a series of super-imposed archaeological horizons. This study shows that site-specific paleo-landscape reconstructions should play an important role in understanding regional variation among hominin occupations and in extrapolating long-term behavioral patterns during the Middle Pleistocene.     

A computerized database-scan to identify c-MYC targets

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease caused by the expansion of a polyglutamine tract in the protein ataxin-7, a protein of unknown function. In order to analyze the expression pattern of wild type ataxin-7 in detail, the murine SCA7 gene homolog was cloned and the expression pattern in mice analyzed. The SCA7 mouse and human gene exhibit a high degree of identity at both DNA (88.2%) and protein (88.7%) level. The CAG repeat region, known to be polymorphic in man, is conserved in mouse but contained only five repeats in all mouse strains analyzed. The arrestin homology domain and the nuclear localization signal found in human ataxin-7 is also conserved in the murine homolog. Expression of ataxin-7 was detected during mouse embryonic development and in all adult mouse tissues examined by northern and western blots. In brain, immunohistological staining revealed an ataxin-7 expression pattern similar to that in human, with ataxin-7 expression in cerebellum, several brainstem nuclei, cerebral cortex and hippocampus. Our data show high conservation of ataxin-7 both structurally and at the level of expression, suggesting a conserved role for the protein in mice and humans.     

Isolation and functional expression of the bop gene from Halobiforma lacisalsi

A novel bop gene was described from Halobiforma lacisalsi strain AJ5^T, an extremely halophilic archaeon isolated from Ayakekum Lake, China. Following six rounds of PCR amplification based on the conserved fragment of the bop gene, the complete sequence of the bop gene, including the 5′ and 3′ flanking regions of the conserved fragment, was obtained by the ligation-mediated PCR amplification (LPA) approach. The data presented provide us with further insight into the distribution of bop-like genes in the family Halobacteriaceae. This is the first example of a bop-like gene in halophiles found in the high-pH environment. Alignment and hydropathy analysis of the deduced amino acid sequence identified the conserved functional sites as well as some variations compared with other bacterio-opsins. Molecular phylogenetic analysis revealed the position of the bacterio-opsin of strain AJ5, which is closest to that of Haloterrigena sp. arg-4 with 85% identity. In the presence of all-trans retinal, recombinant Escherichia coli cells expressing the gene turned dark purple. The purple membrane from the recombinant E. coli showed maximal absorption at 540 nm.     

Effect of oxygen on the cyanobacterium Oscillatoria limnetica

Oscillatoria limnetica grown photoautotrophically under aerobic or anaerobic conditions contained a single superoxide dismutase (SOD) of identical electrophoretic mobility in both cases. Its activity was cyanide resistant and H₂O₂ sensitive, implicating Fe-SOD. The enzyme level was high in aerobically and low in anaerobically growing cells. Anaerobically grown cells were more sensitive than aerobic to photooxidation, as expressed by bleaching of phycocyanin and disintegration of the trichomes.Abbreviations DCMU 3-(3,4-dichlorophenyl)-1,1-dimethylurea - SOD superoxide dismutase     

The interplay between vaccination and social distancing strategies affects COVID19 population-level outcomes

Social distancing is an effective population-level mitigation strategy to prevent COVID19 propagation but it does not reduce the number of susceptible individuals and bears severe social consequences—a dire situation that can be overcome with the recently developed vaccines. Although a combination of these interventions should provide greater benefits than their isolated deployment, a mechanistic understanding of the interplay between them is missing. To tackle this challenge we developed an age-structured deterministic model in which vaccines are deployed during the pandemic to individuals who do not show symptoms. The model allows for flexible and dynamic prioritization strategies with shifts between target groups. We find a strong interaction between social distancing and vaccination in their effect on the proportion of hospitalizations. In particular, prioritizing vaccines to elderly (60+) before adults (20-59) is more effective when social distancing is applied to adults or uniformly. In addition, the temporal reproductive number R_t is only affected by vaccines when deployed at sufficiently high rates and in tandem with social distancing. Finally, the same reduction in hospitalization can be achieved via different combination of strategies, giving decision makers flexibility in choosing public health policies. Our study provides insights into the factors that affect vaccination success and provides methodology to test different intervention strategies in a way that will align with ethical guidelines.