102 research outputs found
Signatures of arithmetic simplicity in metabolic network architecture
Metabolic networks perform some of the most fundamental functions in living
cells, including energy transduction and building block biosynthesis. While
these are the best characterized networks in living systems, understanding
their evolutionary history and complex wiring constitutes one of the most
fascinating open questions in biology, intimately related to the enigma of
life's origin itself. Is the evolution of metabolism subject to general
principles, beyond the unpredictable accumulation of multiple historical
accidents? Here we search for such principles by applying to an artificial
chemical universe some of the methodologies developed for the study of genome
scale models of cellular metabolism. In particular, we use metabolic flux
constraint-based models to exhaustively search for artificial chemistry
pathways that can optimally perform an array of elementary metabolic functions.
Despite the simplicity of the model employed, we find that the ensuing pathways
display a surprisingly rich set of properties, including the existence of
autocatalytic cycles and hierarchical modules, the appearance of universally
preferable metabolites and reactions, and a logarithmic trend of pathway length
as a function of input/output molecule size. Some of these properties can be
derived analytically, borrowing methods previously used in cryptography. In
addition, by mapping biochemical networks onto a simplified carbon atom
reaction backbone, we find that several of the properties predicted by the
artificial chemistry model hold for real metabolic networks. These findings
suggest that optimality principles and arithmetic simplicity might lie beneath
some aspects of biochemical complexity
Whole-Genome Sequencing of a Single Proband Together with Linkage Analysis Identifies a Mendelian Disease Gene
Although more than 2,400 genes have been shown to contain variants that cause Mendelian disease, there are still several thousand such diseases yet to be molecularly defined. The ability of new whole-genome sequencing technologies to rapidly indentify most of the genetic variants in any given genome opens an exciting opportunity to identify these disease genes. Here we sequenced the whole genome of a single patient with the dominant Mendelian disease, metachondromatosis (OMIM 156250), and used partial linkage data from her small family to focus our search for the responsible variant. In the proband, we identified an 11 bp deletion in exon four of PTPN11, which alters frame, results in premature translation termination, and co-segregates with the phenotype. In a second metachondromatosis family, we confirmed our result by identifying a nonsense mutation in exon 4 of PTPN11 that also co-segregates with the phenotype. Sequencing PTPN11 exon 4 in 469 controls showed no such protein truncating variants, supporting the pathogenicity of these two mutations. This combination of a new technology and a classical genetic approach provides a powerful strategy to discover the genes responsible for unexplained Mendelian disorders
TESS discovery of a super-Earth and two sub-Neptunes orbiting the bright, nearby, Sun-like star HD 22946
We report the Transiting Exoplanet Survey Satellite (TESS) discovery of a
three-planet system around the bright Sun-like star HD~22946(V=8.3 mag),also
known as TIC~100990000, located 63 parsecs away.The system was observed by TESS
in Sectors 3, 4, 30 and 31 and two planet candidates, labelled TESS Objects of
Interest (TOIs) 411.01 (planet ) and 411.02 (planet ), were identified on
orbits of 9.57 and 4.04 days, respectively. In this work, we validate the two
planets and recover an additional single transit-like signal in the light
curve, which suggests the presence of a third transiting planet with a longer
period of about 46 days.We assess the veracity of the TESS transit signals and
use follow-up imaging and time series photometry to rule out false positive
scenarios, including unresolved binary systems, nearby eclipsing binaries or
background/foreground stars contaminating the light curves. Parallax
measurements from Gaia EDR3, together with broad-band photometry and
spectroscopic follow-up by TFOP allowed us to constrain the stellar parameters
of TOI-411, including its radius of. Adopting this value,
we determined the radii for the three exoplanet candidates and found that
planet is a super-Earth, with a radius of , while
planet and are sub-Neptunian planets, with radii
of and respectively. By using
dynamical simulations, we assessed the stability of the system and evaluated
the possibility of the presence of other undetected, non-transiting planets by
investigating its dynamical packing. We find that the system is dynamically
stable and potentially unpacked, with enough space to host at least one more
planet between and .(Abridged)Comment: 21 pages, 12 figures. Accepted for publication on A&
Auditory conflict and congruence in frontotemporal dementia.
Impaired analysis of signal conflict and congruence may contribute to diverse socio-emotional symptoms in frontotemporal dementias, however the underlying mechanisms have not been defined. Here we addressed this issue in patients with behavioural variant frontotemporal dementia (bvFTD; n = 19) and semantic dementia (SD; n = 10) relative to healthy older individuals (n = 20). We created auditory scenes in which semantic and emotional congruity of constituent sounds were independently probed; associated tasks controlled for auditory perceptual similarity, scene parsing and semantic competence. Neuroanatomical correlates of auditory congruity processing were assessed using voxel-based morphometry. Relative to healthy controls, both the bvFTD and SD groups had impaired semantic and emotional congruity processing (after taking auditory control task performance into account) and reduced affective integration of sounds into scenes. Grey matter correlates of auditory semantic congruity processing were identified in distributed regions encompassing prefrontal, parieto-temporal and insular areas and correlates of auditory emotional congruity in partly overlapping temporal, insular and striatal regions. Our findings suggest that decoding of auditory signal relatedness may probe a generic cognitive mechanism and neural architecture underpinning frontotemporal dementia syndromes
The Characterization of Twenty Sequenced Human Genomes
We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten “case” genomes from individuals with severe hemophilia A and ten “control” genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs) discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways
Another Shipment of Six Short-Period Giant Planets from TESS
We present the discovery and characterization of six short-period, transiting
giant planets from NASA's Transiting Exoplanet Survey Satellite (TESS) --
TOI-1811 (TIC 376524552), TOI-2025 (TIC 394050135), TOI-2145 (TIC 88992642),
TOI-2152 (TIC 395393265), TOI-2154 (TIC 428787891), & TOI-2497 (TIC 97568467).
All six planets orbit bright host stars (8.9 <G< 11.8, 7.7 <K< 10.1). Using a
combination of time-series photometric and spectroscopic follow-up observations
from the TESS Follow-up Observing Program (TFOP) Working Group, we have
determined that the planets are Jovian-sized (R = 1.00-1.45 R),
have masses ranging from 0.92 to 5.35 M, and orbit F, G, and K stars
(4753 T 7360 K). We detect a significant orbital eccentricity
for the three longest-period systems in our sample: TOI-2025 b (P = 8.872 days,
= ), TOI-2145 b (P = 10.261 days, =
), and TOI-2497 b (P = 10.656 days, =
). TOI-2145 b and TOI-2497 b both orbit subgiant host
stars (3.8 g 4.0), but these planets show no sign of inflation
despite very high levels of irradiation. The lack of inflation may be explained
by the high mass of the planets; M (TOI-2145
b) and M (TOI-2497 b). These six new discoveries
contribute to the larger community effort to use {\it TESS} to create a
magnitude-complete, self-consistent sample of giant planets with
well-determined parameters for future detailed studies.Comment: 20 Pages, 6 Figures, 8 Tables, Accepted by MNRA
Management of hypertension and multiple risk factors to enhance cardiovascular health - a feasibility study in Singapore polyclinics
3D: diversity, dynamics, differential testing – a proposed pipeline for analysis of next-generation sequencing T cell repertoire data
- …