The impact of site-specific positive selection on the structurally and functionally important parts of the snake venom Kunitz/BPTI protein family

Biosurfactants, are surface active molecules that can be produced by renewable, industrially scalable biologic processes. DAMP4, a designer biosurfactant, enables the modification of interfaces via genetic or chemical fusion to functional moieties. However, bioconjugation of addressable amines introduces heterogeneity that limits the precision of functionalization as well as the resolution of interfacial characterization. Here we designed DAMP4 variants with cysteine point mutations to allow for site-specific bioconjugation. The DAMP4 variants were shown to retain the structural stability and interfacial activity characteristic of the parent molecule, while permitting efficient and specific conjugation of polyethylene glycol (PEG). PEGylation results in a considerable reduction on the interfacial activity of both single and double mutants. Comparison of conjugates with one or two conjugation sites shows that both the number of conjugates as well as the mass of conjugated material impacts the interfacial activity of DAMP4. As a result, the ability of DAMP4 variants with multiple PEG conjugates to impart colloidal stability on peptide-stabilized emulsions is reduced. We suggest that this is due to constraints on the structure of amphiphilic helices at the interface. Specific and efficient bioconjugation permits the exploration and investigation of the interfacial properties of designer protein biosurfactants with molecular precision. Our findings should therefore inform the design and modification of biosurfactants for their increasing use in industrial processes, and nutritional and pharmaceutical formulations.

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The Search for Natural and Synthetic Inhibitors That Would Complement Antivenoms as Therapeutics for Snakebite Envenoming

Toxins ◽

10.3390/toxins13070451 ◽

2021 ◽

Vol 13 (7) ◽

pp. 451

Author(s):

José María Gutiérrez ◽

Laura-Oana Albulescu ◽

Rachel H. Clare ◽

Nicholas R. Casewell ◽

Tarek Mohamed Abd Abd El-Aziz ◽

...

Keyword(s):

Snake Venom ◽

Serine Proteinase ◽

Global Strategy ◽

World Health ◽

Wide Range ◽

Variable Chemical ◽

Snake Venom Metalloproteinase ◽

Health Organization ◽

The Impact ◽

Natural And Synthetic

A global strategy, under the coordination of the World Health Organization, is being unfolded to reduce the impact of snakebite envenoming. One of the pillars of this strategy is to ensure safe and effective treatments. The mainstay in the therapy of snakebite envenoming is the administration of animal-derived antivenoms. In addition, new therapeutic options are being explored, including recombinant antibodies and natural and synthetic toxin inhibitors. In this review, snake venom toxins are classified in terms of their abundance and toxicity, and priority actions are being proposed in the search for snake venom metalloproteinase (SVMP), phospholipase A2 (PLA2), three-finger toxin (3FTx), and serine proteinase (SVSP) inhibitors. Natural inhibitors include compounds isolated from plants, animal sera, and mast cells, whereas synthetic inhibitors comprise a wide range of molecules of a variable chemical nature. Some of the most promising inhibitors, especially SVMP and PLA2 inhibitors, have been developed for other diseases and are being repurposed for snakebite envenoming. In addition, the search for drugs aimed at controlling endogenous processes generated in the course of envenoming is being pursued. The present review summarizes some of the most promising developments in this field and discusses issues that need to be considered for the effective translation of this knowledge to improve therapies for tackling snakebite envenoming.

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Site-specific N-glycosylation analysis of animal cell culture-derived Zika virus proteins

Scientific Reports ◽

10.1038/s41598-021-84682-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alexander Pralow ◽

Alexander Nikolay ◽

Arnaud Leon ◽

Yvonne Genzel ◽

Erdmann Rapp ◽

...

Keyword(s):

Zika Virus ◽

Animal Cell ◽

Gradient Centrifugation ◽

Viral Envelope ◽

Protein Glycosylation ◽

High Yield ◽

Structural Protein ◽

Site Specific ◽

E Protein ◽

The Impact

AbstractHere, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain. The virus was propagated with high yield in an embryo-derived stem cell line (EB66, Valneva SE), and concentrated by g-force step-gradient centrifugation. Subsequently, the sample was proteolytically digested with different enzymes, measured via a LC–MS/MS-based workflow, and analyzed in a semi-automated way using the in-house developed glyXtoolMS software. The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites. In case of the viral envelope (E) protein, no specific N-glycans could be identified with this method. Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444. This confirmed that this site of the ZIKV E protein is highly N-glycosylated but with very high micro-heterogeneity. Our study clearly demonstrates the progress made towards site-specific N-glycosylation analysis of viral proteins, i.e. for Brazilian ZIKV. It allows to better characterize viral isolates, and to monitor glycosylation of major antigens. The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.

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The influence of riparian woodland on the spatial and temporal variability of stream water temperatures in an upland salmon stream

Hydrology and Earth System Sciences ◽

10.5194/hess-8-449-2004 ◽

2004 ◽

Vol 8 (3) ◽

pp. 449-459 ◽

Cited By ~ 62

Author(s):

I. A. Malcolm ◽

D. M. Hannah ◽

M. J. Donaghy ◽

C. Soulsby ◽

A. F. Youngson

Keyword(s):

Thermal Regime ◽

Temporal Variability ◽

Heat Budget ◽

Riparian Forest ◽

Stream Water ◽

Spatial And Temporal Variability ◽

Substantial Impact ◽

Site Specific ◽

The Impact ◽

Riparian Woodland

Abstract. The spatio-temporal variability of stream water temperatures was investigated at six locations on the Girnock Burn (30km2 catchment), Cairngorms, Scotland over three hydrological years between 1998 and 2002. The key site-specific factors affecting the hydrology and climatology of the sampling points were investigated as a basis for physical process inference. Particular emphasis was placed on assessing the effects of riparian forest in the lower catchment versus the heather moorland riparian zones that are spatially dominant in the upper catchment. The findings were related to river heat budget studies that provided process detail. Gross changes in stream temperature were affected by the annual cycle of incoming solar radiation and seasonal changes in hydrological and climatological conditions. Inter-annual variation in these controlling variables resulted in inter-annual variability in thermal regime. However, more subtle inter-site differences reflected the impact of site-specific characteristics on various components of the river energy budget. Inter-site variability was most apparent at shorter time scales, during the summer months and for higher stream temperatures. Riparian woodland in the lower catchment had a substantial impact on thermal regime, reducing diel variability (over a period of 24 hours) and temperature extremes. Observed inter-site differences are likely to have a substantial effect on freshwater ecology in general and salmonid fish in particular. Keywords: temperature, thermal regime, forest, salmon, hydrology, Girnock Burn, Cairngorm

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Assembly: Performing the materiality of Muslim prayer spaces

Scene ◽

10.1386/scene_00014_1 ◽

2018 ◽

Vol 6 (2) ◽

pp. 133-151 ◽

Cited By ~ 1

Author(s):

Julie Marsh

Keyword(s):

Social Boundaries ◽

Research Project ◽

Site Specific ◽

Specific Research ◽

A Site ◽

The Impact

This article reflects on the significance and impact of Assembly, a site-specific research project made and exhibited in Birmingham Central Mosque, Brick Lane Mosque and Old Kent Road Mosque from 2016 to 2020. Assembly provided an opportunity for Muslims and non-Muslims to experience Jumu’ah prayer first-hand via the site performances, which temporarily dissolved the religious/social boundaries of each mosque. Each performance highlighted the differences and relations between each site, furthering ideas of performativity in Muslim prayer spaces. This article summarizes the impact reported by each mosque community as well as reflecting upon the relationships built within the wider community.

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WATER VAPOUR WEIGHTED MEAN TEMPERATURE MODEL FOR GPS-DERIVED INTEGRATED WATER VAPOUR IN PENINSULAR MALAYSIA

ISPRS - International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences ◽

10.5194/isprs-archives-xlii-4-w5-127-2017 ◽

2017 ◽

Vol XLII-4/W5 ◽

pp. 127-135 ◽

Cited By ~ 1

Author(s):

T. A. Musa ◽

M. H. Mazlan ◽

Y. D. Opaluwa ◽

I. A. Musliman ◽

Z. M. Radzi

Keyword(s):

Water Vapour ◽

Diurnal Cycle ◽

Specific Model ◽

Regional Model ◽

Peninsular Malaysia ◽

Site Specific ◽

Weighted Mean Temperature ◽

Integrated Water Vapour ◽

Relationship Of ◽

The Impact

This paper presents the development of TM model by using the radiosonde stations from Peninsular Malaysia. Two types of TM model were developed; site-specific and regional models. The result revealed that the estimation from site-specific model has small improvement compared to the regional model, indicating that the regional model is adequately to use in estimation of GPS-derived IWV over Peninsular Malaysia. Meanwhile, this study found that the diurnal cycle of TS has influenced the TM&ndash;TS relationship. The separation between daytime and nighttime observation can improve the relationship of TM&ndash;TS. However, the impact of diurnal cycle to IWV estimation is less than 1&thinsp;%. The TM model from Global and Tropic also been evaluated. The Tropic TM model is superior to be utilized as compared to the Global TM model.

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Selection shapes the landscape of functional variation in wild house mice

BMC Biology ◽

10.1186/s12915-021-01165-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Raman Akinyanju Lawal ◽

Uma P. Arora ◽

Beth L. Dumont

Keyword(s):

Positive Selection ◽

Significant Proportion ◽

Wild Mouse ◽

House Mice ◽

Functional Variation ◽

Disease Associated Genes ◽

Functional Alleles ◽

The Impact ◽

Mouse Genetic

Abstract Background Through human-aided dispersal over the last ~ 10,000 years, house mice (Mus musculus) have recently colonized diverse habitats across the globe, promoting the emergence of new traits that confer adaptive advantages in distinct environments. Despite their status as the premier mammalian model system, the impact of this demographic and selective history on the global patterning of disease-relevant trait variation in wild mouse populations is poorly understood. Results Here, we leveraged 154 whole-genome sequences from diverse wild house mouse populations to survey the geographic organization of functional variation and systematically identify signals of positive selection. We show that a significant proportion of wild mouse variation is private to single populations, including numerous predicted functional alleles. In addition, we report strong signals of positive selection at many genes associated with both complex and Mendelian diseases in humans. Notably, we detect a significant excess of selection signals at disease-associated genes relative to null expectations, pointing to the important role of adaptation in shaping the landscape of functional variation in wild mouse populations. We also uncover strong signals of selection at multiple genes involved in starch digestion, including Mgam and Amy1. We speculate that the successful emergence of the human-mouse commensalism may have been facilitated, in part, by dietary adaptations at these loci. Finally, our work uncovers multiple cryptic structural variants that manifest as putative signals of positive selection, highlighting an important and under-appreciated source of false-positive signals in genome-wide selection scans. Conclusions Overall, our findings highlight the role of adaptation in shaping wild mouse genetic variation at human disease-associated genes. Our work also highlights the biomedical relevance of wild mouse genetic diversity and underscores the potential for targeted sampling of mice from specific populations as a strategy for developing effective new mouse models of both rare and common human diseases.

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