Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research

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

NGTS discovery of a highly inflated Saturn-mass planet and a highly irradiated hot Jupiter

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

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

NGTS-13b: A hot 4.8 Jupiter-mass planet transiting a subgiant star

We report the discovery of the massive hot Jupiter NGTS-13b by the Next Generation Transit Survey (NGTS). The V = 12.7 host star is likely in the subgiant evolutionary phase with log g$_{*}$ = 4.04 $\pm$ 0.05, T$_{eff}$ = 5819 $\pm$ 73 K, M$_{*}$ = 1.30$^{+0.11}_{-0.18}$ M$_{\odot}$, and R$_{*}$ = 1.79 $\pm$ 0.06 R$_{\odot}$. NGTS detected a transiting planet with a period of P = 4.12 days around the star, which was later validated with the Transiting Exoplanet Survey Satellite (TESS; TIC 454069765). We confirm the planet using radial velocities from the CORALIE spectrograph. Using NGTS and TESS full-frame image photometry combined with CORALIE radial velocities we determine NGTS-13b to have a radius of R$_{P}$ = 1.142 $\pm$ 0.046 R$_{Jup}$, mass of M$_{P}$ = 4.84 $\pm$ 0.44 M$_{Jup}$ and eccentricity e = 0.086 $\pm$ 0.034. Some previous studies suggest that $\sim$4 M$_{Jup}$ may be a border between two separate formation scenarios (e.g., core accretion and disk instability) and that massive giant planets share similar formation mechanisms as lower-mass brown dwarfs. NGTS-13b is just above 4 M$_{Jup}$ making it an important addition to the statistical sample needed to understand the differences between various classes of substellar companions. The high metallicity, [Fe/H] = 0.25 $\pm$ 0.17, of NGTS-13 does not support previous suggestions that massive giants are found preferentially around lower metallicity host stars, but NGTS-13b does support findings that more massive and evolved hosts may have a higher occurrence of close-in massive planets than lower-mass unevolved stars

Planet Hunters NGTS: New Planet Candidates from a Citizen Science Search of the Next Generation Transit Survey Public Data

We present the results from the first two years of the Planet Hunters Next Generation Transit Survey (NGTS) citizen science project, which searches for transiting planet candidates in data from the NGTS by enlisting the help of members of the general public. Over 8000 registered volunteers reviewed 138,198 light curves from the NGTS Public Data Releases 1 and 2. We utilize a user weighting scheme to combine the classifications of multiple users to identify the most promising planet candidates not initially discovered by the NGTS team. We highlight the five most interesting planet candidates detected through this search, which are all candidate short-period giant planets. This includes the TIC-165227846 system that, if confirmed, would be the lowest-mass star to host a close-in giant planet. We assess the detection efficiency of the project by determining the number of confirmed planets from the NASA Exoplanet Archive and TESS Objects of Interest (TOIs) successfully recovered by this search and find that 74% of confirmed planets and 63% of TOIs detected by NGTS are recovered by the Planet Hunters NGTS project. The identification of new planet candidates shows that the citizen science approach can provide a complementary method to the detection of exoplanets with ground-based surveys such as NGTS

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

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

Identifying Changes in Selective Constraints: Host Shifts in Influenza

The natural reservoir of Influenza A is waterfowl. Normally, waterfowl viruses are not adapted to infect and spread in the human population. Sometimes, through reassortment or through whole host shift events, genetic material from waterfowl viruses is introduced into the human population causing worldwide pandemics. Identifying which mutations allow viruses from avian origin to spread successfully in the human population is of great importance in predicting and controlling influenza pandemics. Here we describe a novel approach to identify such mutations. We use a sitewise non-homogeneous phylogenetic model that explicitly takes into account differences in the equilibrium frequencies of amino acids in different hosts and locations. We identify 172 amino acid sites with strong support and 518 sites with moderate support of different selection constraints in human and avian viruses. The sites that we identify provide an invaluable resource to experimental virologists studying adaptation of avian flu viruses to the human host. Identification of the sequence changes necessary for host shifts would help us predict the pandemic potential of various strains. The method is of broad applicability to investigating changes in selective constraints when the timing of the changes is known

Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways

Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE), we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37°C), avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human proximal airways (32°C). These data support the hypothesis that avian influenza viruses, ordinarily adapted to the temperature of the avian enteric tract (40°C), rarely infect humans, in part due to differences in host airway regional temperatures. Previously, a critical residue at position 627 in the avian influenza virus polymerase subunit, PB2, was identified as conferring temperature-dependency in mammalian cells. Here, we use reverse genetics to show that avianization of residue 627 attenuates a human virus, but does not account for the different infection between 32°C and 37°C. To determine the mechanism of temperature restriction of avian influenza viruses in HAE at 32°C, we generated recombinant human influenza viruses in either the A/Victoria/3/75 (H3N2) or A/PR/8/34 (H1N1) genetic background that contained avian or avian-like glycoproteins. Two of these viruses, A/Victoria/3/75 with L226Q and S228G mutations in hemagglutinin (HA) and neuraminidase (NA) from A/Chick/Italy/1347/99 and A/PR/8/34 containing the H7 and N1 from A/Chick/Italy/1347/99, exhibited temperature restriction approaching that of wholly avian influenza viruses. These data suggest that influenza viruses bearing avian or avian-like surface glycoproteins have a reduced capacity to establish productive infection at the temperature of the human proximal airways. This temperature restriction may limit zoonotic transmission of avian influenza viruses and suggests that adaptation of avian influenza viruses to efficient infection at 32°C may represent a critical evolutionary step enabling human-to-human transmission