A Critical Tryptophan and Ca2+ in Activation and Catalysis of TPPI, the Enzyme Deficient in Classic Late-Infantile Neuronal Ceroid Lipofuscinosis

Tripeptidyl aminopeptidase I (TPPI) is a crucial lysosomal enzyme that is deficient in the fatal neurodegenerative disorder called classic late-infantile neuronal ceroid lipofuscinosis (LINCL). It is involved in the catabolism of proteins in the lysosomes. Recent X-ray crystallographic studies have provided insights into the structural/functional aspects of TPPI catalysis, and indicated presence of an octahedrally coordinated Ca(2+).Purified precursor and mature TPPI were used to study inhibition by NBS and EDTA using biochemical and immunological approaches. Site-directed mutagenesis with confocal imaging technique identified a critical W residue in TPPI activity, and the processing of precursor into mature enzyme.NBS is a potent inhibitor of the purified TPPI. In mammalian TPPI, W542 is critical for tripeptidyl peptidase activity as well as autocatalysis. Transfection studies have indicated that mutants of the TPPI that harbor residues other than W at position 542 have delayed processing, and are retained in the ER rather than transported to lysosomes. EDTA inhibits the autocatalytic processing of the precursor TPPI.We propose that W542 and Ca(2+) are critical for maintaining the proper tertiary structure of the precursor proprotein as well as the mature TPPI. Additionally, Ca(2+) is necessary for the autocatalytic processing of the precursor protein into the mature TPPI. We have identified NBS as a potent TPPI inhibitor, which led in delineating a critical role for W542 residue. Studies with such compounds will prove valuable in identifying the critical residues in the TPPI catalysis and its structure-function analysis

NGTS discovery of a highly inflated Saturn-mass planet and a highly irradiated hot Jupiter: NGTS-26 b and NGTS-27 b

We report the discovery of two new transiting giant exoplanets NGTS-26 b and NGTS-27 b by the Next Generation Transit Survey (NGTS). NGTS-26 b orbits around a G6-type main sequence star every 4.52 days. It has a mass of 0.29-0.06+0.07 MJup and a radius of 1.33-0.05+0.06 RJup making it a Saturn-mass planet with a highly inflated radius. NGTS-27 b orbits around a slightly evolved G3-type star every 3.37 days. It has a mass of 0.59-0.07+0.10 MJup and a radius of 1.40±0.04 RJup, making it a relatively standard hot Jupiter. The transits of these two planetary systems were re-observed and confirmed in photometry by the SAAO 1.0-m telescope, 1.2-m Euler Swiss telescope as well as the TESS spacecraft, and their masses were derived spectroscopically by the CORALIE, FEROS and HARPS spectrographs. Both giant exoplanets are highly irradiated by their host stars and present an anomalously inflated radius, especially NGTS-26 b which is one of the largest objects among peers of similar mass

Habitat Association and Seasonality in a Mosaic and Bimodal Hybrid Zone between Chorthippus brunneus and C. jacobsi (Orthoptera: Acrididae)

Understanding why some hybrid zones are bimodal and others unimodal can aid in identifying barriers to gene exchange following secondary contact. The hybrid zone between the grasshoppers Chorthippus brunneus and C. jacobsi contains a mix of allopatric parental populations and inter-mingled bimodal and unimodal sympatric populations, and provides an ideal system to examine the roles of local selection and gene flow between populations in maintaining bimodality. However, it is first necessary to confirm, over a larger spatial scale, previously identified associations between population composition and season and habitat. Here we use cline-fitting of one morphological and one song trait along two valley transects, and intervening mountains, to confirm previously identified habitat associations (mountain versus valley) and seasonal changes in population composition. As expected from previous findings of studies on a smaller spatial scale, C. jacobsi dominated mountain habitats and mixed populations dominated valleys, and C. brunneus became more prevalent in August. Controlling for habitat and incorporating into the analysis seasonal changes in cline parameters and the standard errors of parental trait values revealed wider clines than previous studies (best estimates of 6.4 to 24.5 km in our study versus 2.8 to 4.7 km in previous studies) and increased percentage of trait variance explained (52.7% and 61.5% for transects 1 and 2 respectively, versus 17.6%). Revealing such strong and consistent patterns within a complex hybrid zone will allow more focused examination of the causes of variation in bimodality in mixed populations, in particular the roles of local selection versus habitat heterogeneity and gene flow between differentiated populations

Fatal Cases of Influenza A(H3N2) in Children: Insights from Whole Genome Sequence Analysis

During the Northern Hemisphere winter of 2003–2004 the emergence of a novel influenza antigenic variant, A/Fujian/411/2002-like(H3N2), was associated with an unusually high number of fatalities in children. Seventeen fatal cases in the UK were laboratory confirmed for Fujian/411-like viruses. To look for phylogenetic patterns and genetic markers that might be associated with increased virulence, sequencing and phylogenetic analysis of the whole genomes of 63 viruses isolated from fatal cases and non fatal “control” cases was undertaken. The analysis revealed the circulation of two main genetic groups, I and II, both of which contained viruses from fatal cases. No associated amino acid substitutions could be linked with an exclusive or higher occurrence in fatal cases. The Fujian/411-like viruses in genetic groups I and II completely displaced other A(H3N2) viruses, but they disappeared after 2004. This study shows that two A(H3N2) virus genotypes circulated exclusively during the winter of 2003–2004 in the UK and caused an unusually high number of deaths in children. Host factors related to immune state and differences in genetic background between patients may also play important roles in determining the outcome of an influenza infection

Ecological Niche Dimensionality and the Evolutionary Diversification of Stick Insects

The degree of phenotypic divergence and reproductive isolation between taxon pairs can vary quantitatively, and often increases as evolutionary divergence proceeds through various stages, from polymorphism to population differentiation, ecotype and race formation, speciation, and post-speciational divergence. Although divergent natural selection promotes divergence, it does not always result in strong differentiation. For example, divergent selection can fail to complete speciation, and distinct species pairs sometimes collapse (‘speciation in reverse’). Widely-discussed explanations for this variability concern genetic architecture, and the geographic arrangement of populations. A less-explored possibility is that the degree of phenotypic and reproductive divergence between taxon pairs is positively related to the number of ecological niche dimensions (i.e., traits) subject to divergent selection. Some data supporting this idea stem from laboratory experimental evolution studies using Drosophila, but tests from nature are lacking. Here we report results from manipulative field experiments in natural populations of herbivorous Timema stick insects that are consistent with this ‘niche dimensionality’ hypothesis. In such insects, divergent selection between host plants might occur for cryptic colouration (camouflage to evade visual predation), physiology (to detoxify plant chemicals), or both of these niche dimensions. We show that divergent selection on the single niche dimension of cryptic colouration can result in ecotype formation and intermediate levels of phenotypic and reproductive divergence between populations feeding on different hosts. However, greater divergence between a species pair involved divergent selection on both niche dimensions. Although further replication of the trends reported here is required, the results suggest that dimensionality of selection may complement genetic and geographic explanations for the degree of diversification in nature

NGTS-11 b (TOI-1847 b): A Transiting Warm Saturn Recovered from a TESS Single-transit Event

We report the discovery of NGTS-11 b (=TOI-1847 b), a transiting Saturn in a 35.46-day orbit around a mid K-type star (Teff=5050 K). We initially identified the system from a single-transit event in a TESS full-frame image light-curve. Following seventy-nine nights of photometric monitoring with an NGTS telescope, we observed a second full transit of NGTS-11 b approximately one year after the TESS single-transit event. The NGTS transit confirmed the parameters of the transit signal and restricted the orbital period to a set of 13 discrete periods. We combined our transit detections with precise radial velocity measurements to determine the true orbital period and measure the mass of the planet. We find NGTS-11 b has a radius of 0.817+0.028-0.032 $R_J$, a mass of 0.344+0.092-0.073 $M_J$, and an equilibrium temperature of just 435+34-32 K, making it one of the coolest known transiting gas giants. NGTS-11 b is the first exoplanet to be discovered after being initially identified as a TESS single-transit event, and its discovery highlights the power of intense photometric monitoring in recovering longer-period transiting exoplanets from single-transit events

The N-Terminal Region of the PA Subunit of the RNA Polymerase of Influenza A/HongKong/156/97 (H5N1) Influences Promoter Binding

BACKGROUND: The RNA polymerase of influenza virus is a heterotrimeric complex of PB1, PB2 and PA subunits which cooperate in the transcription and replication of the viral genome. Previous research has shown that the N-terminal region of the PA subunit of influenza A/WSN/33 (H1N1) virus is involved in promoter binding. METHODOLOGY/PRINCIPAL FINDINGS: Here we extend our studies of the influenza RNA polymerase to that of influenza strains A/HongKong/156/97 (H5N1) and A/Vietnam/1194/04 (H5N1). Both H5N1 strains, originally isolated from patients in 1997 and 2004, showed significantly higher polymerase activity compared with two classical human strains, A/WSN/33 (H1N1) and A/NT/60/68 (H3N2) in vitro. This increased polymerase activity correlated with enhanced promoter binding. The N-terminal region of the PA subunit was the major determinant of this enhanced promoter activity. CONCLUSIONS/SIGNIFICANCE: Overall we suggest that the N-terminal region of the PA subunit of two recent H5N1 strains can influence promoter binding and we speculate this may be a factor in their virulence

An ultrahot Neptune in the Neptune desert

About one out of 200 Sun-like stars has a planet with an orbital period shorter than one day: an ultra-short-period planet (Sanchis-ojeda et al. 2014; Winn et al. 2018). All of the previously known ultra-short-period planets are either hot Jupiters, with sizes above 10 Earth radii (Re), or apparently rocky planets smaller than 2 Re. Such lack of planets of intermediate size (the "hot Neptune desert") has been interpreted as the inability of low-mass planets to retain any hydrogen/helium (H/He) envelope in the face of strong stellar irradiation. Here, we report the discovery of an ultra-short-period planet with a radius of 4.6 Re and a mass of 29 Me, firmly in the hot Neptune desert. Data from the Transiting Exoplanet Survey Satellite (Ricker et al. 2015) revealed transits of the bright Sun-like star \starname\, every 0.79 days. The planet's mean density is similar to that of Neptune, and according to thermal evolution models, it has a H/He-rich envelope constituting 9.0^(+2.7)_(-2.9)% of the total mass. With an equilibrium temperature around 2000 K, it is unclear how this "ultra-hot Neptune" managed to retain such an envelope. Follow-up observations of the planet's atmosphere to better understand its origin and physical nature will be facilitated by the star's brightness (Vmag=9.8)

Citizen science breathes new life into participatory agricultural research : A review

Participatory research can improve the efficiency, effectiveness, and scope of research processes, and foster social inclusion, empowerment and sustainability. Yet despite four decades of agricultural research institutions exploring and developing methods for participatory research, it has never become mainstream in the agricultural technology development cycle. Citizen science promises an innovative approach to participation in research, using the unique facilities of new digital technologies, but its potential in agricultural research participation has not been systematically probed. To this end, we conducted a critical literature review. We found that citizen science opens up four opportunities for creatively reshaping research: i) new possibilities for interdisciplinary collaboration, ii) rethinking configurations of socio-computational systems, iii) research on democratization of science more broadly, and iv) new accountabilities. Citizen science also brings a fresh perspective on the barriers to institutionalizing participation in the agricultural sciences. Specifically, we show how citizen science can reconfigure cost-motivation-accountability combinations using digital tools, open up a larger conceptual space of experimentation, and stimulate new collaborations. With appropriate and persistent institutional support and investment, citizen science can therefore have a lasting impact on how agricultural science engages with farming communities and wider society, and more fully realize the promises of participation

data protection and ethical issues in european p5 ehealth

In spite of its promise to significantly ameliorate health and care practices, the momentous rise of eHealth technologies has been fraught with significant ethical and societal concerns. Focusing on the unfolding of eHealth within the European Union, this contribution will explore its underpinning regulatory landscape with regard to data protection, focusing on the impact of the recently enforced Regulation (EU) 2016/679, also known as the General Data Protection Regulation. In addition, this chapter will chart relevant ethical issues related to the emergence of novel eHealth technologies. Finally, the conclusion will briefly explore ethical issues and their solutions in the light of the P5 approach