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"Hoffmann, M"
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Dissecting cell identity via network inference and in silico gene perturbation
Cell identity is governed by the complex regulation of gene expression, represented as gene-regulatory networks
1
. Here we use gene-regulatory networks inferred from single-cell multi-omics data to perform in silico transcription factor perturbations, simulating the consequent changes in cell identity using only unperturbed wild-type data. We apply this machine-learning-based approach, CellOracle, to well-established paradigms—mouse and human haematopoiesis, and zebrafish embryogenesis—and we correctly model reported changes in phenotype that occur as a result of transcription factor perturbation. Through systematic in silico transcription factor perturbation in the developing zebrafish, we simulate and experimentally validate a previously unreported phenotype that results from the loss of
noto
, an established notochord regulator. Furthermore, we identify an axial mesoderm regulator,
lhx1a
. Together, these results show that CellOracle can be used to analyse the regulation of cell identity by transcription factors, and can provide mechanistic insights into development and differentiation.
A machine-learning-based strategy called CellOracle combines computational perturbation with modelling of gene-regulatory networks to analyse how cell identity is regulated by transcription factors, and correctly predicts phenotypic changes after transcription factor perturbation in the developing zebrafish.
Journal Article
Topological–chiral magnetic interactions driven by emergent orbital magnetism
Two hundred years ago, Ampère discovered that electric loops in which currents of electrons are generated by a penetrating magnetic field can mutually interact. Here we show that Ampère’s observation can be transferred to the quantum realm of interactions between triangular plaquettes of spins on a lattice, where the electrical currents at the atomic scale are associated with the orbital motion of electrons in response to the non-coplanarity of neighbouring spins playing the role of a magnetic field. The resulting topological orbital moment underlies the relation of the orbital dynamics with the topology of the spin structure. We demonstrate that the interactions of the topological orbital moments with each other and with the spins form a new class of magnetic interactions
−
topological–chiral interactions
−
which can dominate over the Dzyaloshinskii–Moriya interaction, thus opening a path for realizing new classes of chiral magnetic materials with three-dimensional magnetization textures such as hopfions.
The motion of electrons in a complex magnetic background may generate novel magnetic interactions. Here, Grytsiuk et al. report that a peculiar orbital motion of electrons in response to a non-coplanarity of neighbouring spins leads to a topological orbital moment, which further gives rise to a new class of magnetic interactions.
Journal Article
Implications of agricultural transitions and urbanization for ecosystem services
Historically, farmers and hunter-gatherers relied directly on ecosystem services, which they both exploited and enjoyed. Urban populations still rely on ecosystems, but prioritize non-ecosystem services (socioeconomic). Population growth and densification increase the scale and change the nature of both ecosystem- and non-ecosystem-service supply and demand, weakening direct feedbacks between ecosystems and societies and potentially pushing social–ecological systems into traps that can lead to collapse. The interacting and mutually reinforcing processes of technological change, population growth and urbanization contribute to over-exploitation of ecosystems through complex feedbacks that have important implications for sustainable resource use.
Journal Article
Light-Induced Superconductivity in a Stripe-Ordered Cuprate
One of the most intriguing features of some high-temperature cuprate superconductors is the interplay between one-dimensional \"striped\" spin order and charge order, and superconductivity. We used mid-infrared femtosecond pulses to transform one such stripe-ordered compound, nonsuperconducting La₁.₆₇₅Eu₀.₂Sr₀.₁₂₅CuO₄, into a transient three-dimensional superconductor. The emergence of coherent interlayer transport was evidenced by the prompt appearance of a Josephson plasma resonance in the c-axis optical properties. An upper limit for the time scale needed to form the superconducting phase is estimated to be 1 to 2 picoseconds, which is significantly faster than expected. This places stringent new constraints on our understanding of stripe order and its relation to superconductivity.
Journal Article
Terahertz electric-field-driven dynamical multiferroicity in SrTiO3
The emergence of collective order in matter is among the most fundamental and intriguing phenomena in physics. In recent years, the dynamical control and creation of novel ordered states of matter not accessible in thermodynamic equilibrium is receiving much attention
1
,
2
,
3
,
4
,
5
–
6
. The theoretical concept of dynamical multiferroicity has been introduced to describe the emergence of magnetization due to time-dependent electric polarization in non-ferromagnetic materials
7
,
8
. In simple terms, the coherent rotating motion of the ions in a crystal induces a magnetic moment along the axis of rotation. Here we provide experimental evidence of room-temperature magnetization in the archetypal paraelectric perovskite SrTiO
3
due to this mechanism. We resonantly drive the infrared-active soft phonon mode with an intense circularly polarized terahertz electric field and detect the time-resolved magneto-optical Kerr effect. A simple model, which includes two coupled nonlinear oscillators whose forces and couplings are derived with ab initio calculations using self-consistent phonon theory at a finite temperature
9
, reproduces qualitatively our experimental observations. A quantitatively correct magnitude was obtained for the effect by also considering the phonon analogue of the reciprocal of the Einstein–de Haas effect, which is also called the Barnett effect, in which the total angular momentum from the phonon order is transferred to the electronic one. Our findings show a new path for the control of magnetism, for example, for ultrafast magnetic switches, by coherently controlling the lattice vibrations with light.
We demonstrate the emergence of magnetism induced by a terahertz electric field in SrTiO
3
.
Journal Article
Optically enhanced coherent transport in YBa2Cu3O6.5 by ultrafast redistribution of interlayer coupling
Nonlinear optical excitation of infrared active lattice vibrations has been shown to melt magnetic or orbital orders and to transform insulators into metals. In cuprates, this technique has been used to remove charge stripes and promote superconductivity, acting in a way opposite to static magnetic fields. Here, we show that excitation of large-amplitude apical oxygen distortions in the cuprate superconductor YBa
2
Cu
3
O
6.5
promotes highly unconventional electronic properties. Below the superconducting transition temperature (
T
c
= 50 K) inter-bilayer coherence is transiently enhanced at the expense of intra-bilayer coupling. Strikingly, even above
T
c
a qualitatively similar effect is observed up to room temperature, with transient inter-bilayer coherence emerging from the incoherent ground state and similar transfer of spectral weight from high to low frequency. These observations are compatible with previous reports of an inhomogeneous normal state that retains important properties of a superconductor, in which light may be melting competing orders or dynamically synchronizing the interlayer phase. The transient redistribution of coherence discussed here could lead to new strategies to enhance superconductivity in steady state.
Mode-selective vibrational excitations can be used to transiently induce a range of phenomena in strongly correlated states of matter. It is now shown that by exciting apical oxygen distortions in the cuprate system YBa
2
Cu
3
O
6.5
, an unusual photoconductive effect is induced both at low and at high temperatures.
Journal Article
Reprogramming to recover youthful epigenetic information and restore vision
Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity
1
–
3
. Changes to DNA methylation patterns over time form the basis of ageing clocks
4
, but whether older individuals retain the information needed to restore these patterns—and, if so, whether this could improve tissue function—is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity
5
–
7
. Using the eye as a model CNS tissue, here we show that ectopic expression of
Oct4
(also known as
Pou5f1
),
Sox2
and
Klf4
genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information—encoded in part by DNA methylation—that can be accessed to improve tissue function and promote regeneration in vivo.
Expression of three Yamanaka transcription factors in mouse retinal ganglion cells restores youthful DNA methylation patterns, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice, suggesting that mammalian tissues retain a record of youthful epigenetic information that can be accessed to improve tissue function.
Journal Article
Is the push-pull paradigm useful to explain rural-urban migration? A case study in Uttarakhand, India
The present study explored the motivation of rural-urban migrants who moved from the Himalaya foothills of Uttarakhand to its capital city, Dehradun. A survey of 100 migrant families reported their socio-economic profile before and after migration, personal and general reasons for migration, problems in the village and in the city, and perception of push- and pull factors. A remote sensing-based analysis of land cover and forest changes was conducted for two villages of the migrants' origin, aiming to link the reasons for migration to land cover changes. This was contextualised by reported large scale changes in forest cover. Major reasons for migration mentioned in this study were education, employment opportunities with the associated income, and facilities. These were perceived as both, push and pull factors, whereas environmental factors ranked very low. Declining environment or agriculture were never mentioned spontaneously as personal reason, and only occasionally as a presumed general reason for migration, but were frequently confirmed as a major problem in the village. Thus, although such problems existed, they seemed not a major driver of rural-urban migration. For most of the respondents their migration resulted in a profound change of livelihoods and significantly improved their socio-economic situation. Land and forest cover around the chosen villages fluctuated by up to 15% with a trend to increasing forest cover in recent years. At the district and state scales, forest cover was rather stable. These results question the narrative of deforestation and environmental degradation in the Himalayas as major push-factors for rural-urban migration in Uttarakhand. Even if environmental constraints were felt, it was rather the differences in socio-economic opportunities (education, employment, facilities) that drove people to migrate to the city. Regarding the push-pull paradigm, we conclude that scenarios of external conditions under which people migrate cannot be evaluated without taking the migrants' attitudes and choices into account.
Journal Article
Rehybridization dynamics into the pericyclic minimum of an electrocyclic reaction imaged in real-time
Electrocyclic reactions are characterized by the concerted formation and cleavage of both σ and π bonds through a cyclic structure. This structure is known as a pericyclic transition state for thermal reactions and a pericyclic minimum in the excited state for photochemical reactions. However, the structure of the pericyclic geometry has yet to be observed experimentally. We use a combination of ultrafast electron diffraction and excited state wavepacket simulations to image structural dynamics through the pericyclic minimum of a photochemical electrocyclic ring-opening reaction in the molecule α-terpinene. The structural motion into the pericyclic minimum is dominated by rehybridization of two carbon atoms, which is required for the transformation from two to three conjugated π bonds. The σ bond dissociation largely happens after internal conversion from the pericyclic minimum to the electronic ground state. These findings may be transferrable to electrocyclic reactions in general.
Electrocyclic reactions proceed through critical geometries, which are known as pericyclic transition states in thermal reactions and pericyclic minima in photochemical reactions. Here, the authors image the structure of a pericyclic minimum in real time using a combination of ultrafast electron diffraction and ab initio dynamics simulations.
Journal Article