Hydrogen bonding underpins the properties of a vast array of systems spanning a wide variety of scientific fields. From the elegance of base pair interactions in DNA to the symmetry of extended ...supramolecular assemblies, hydrogen bonds play an essential role in directing intermolecular forces. Yet fundamental aspects of the hydrogen bond continue to be vigorously debated. Here we use dynamic force microscopy (DFM) to quantitatively map the tip-sample force field for naphthalene tetracarboxylic diimide molecules hydrogen-bonded in two-dimensional assemblies. A comparison of experimental images and force spectra with their simulated counterparts shows that intermolecular contrast arises from repulsive tip-sample interactions whose interpretation can be aided via an examination of charge density depletion across the molecular system. Interpreting DFM images of hydrogen-bonded systems therefore necessitates detailed consideration of the coupled tip-molecule system: analyses based on intermolecular charge density in the absence of the tip fail to capture the essential physical chemistry underpinning the imaging mechanism.
How specific cell types can be directly converted into other distinct cell types is a matter of intense investigation with wide-ranging basic and biomedical implications. Here, we show that removal ...of the histone 3 lysine 27 (H3K27) methyltransferase Polycomb repressor complex 2 (PRC2) permits ectopically expressed, neuron-type-specific transcription factors (“terminal selectors”) to convert Caenorhabditis elegans germ cells directly into specific neuron types. Terminal-selector-induced germ-cell-to-neuron conversion can be observed not only upon genome-wide loss of H3K27 methylation in PRC2(−) animals but also upon genome-wide redistribution of H3K27 methylation patterns in animals that lack the H3K36 methyltransferase MES-4. Manipulation of the H3K27 methylation status not only permits conversion of germ cells into neurons but also permits hlh-1/MyoD-dependent conversion of germ cells into muscle cells, indicating that PRC2 protects the germline from the aberrant execution of multiple distinct somatic differentiation programs. Taken together, our findings demonstrate that the normally multistep process of development from a germ cell via a zygote to a terminally differentiated somatic cell type can be short-cut by providing an appropriate terminal selector transcription factor and manipulating histone methylation patterns.
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► Selector-type transcription factors cannot convert germ cells into neurons or muscle ► Loss of H3K27me3 allows direct, selector-driven germ cell conversion to neurons or muscle ► H3K27me3 redistribution in H3K36me(−) animals also permits germ cell conversion ► Mitotic cycling is not required for induced germ cell conversion
How specific cell types can be directly converted into other distinct cell types is an area of active research. Hobert and colleagues show that loss of a specific chromatin mark permits the direct, transcription-factor-induced reprogramming of germ cells into neurons and muscle. This finding shows that the multistep process of development from a germ cell to a terminally differentiated somatic cell type can be bypassed by providing the right transcription factor and histone methylation pattern.
Ectopic expression of master regulatory transcription factors can reprogram the identity of specific cell types. The effectiveness of such induced cellular reprogramming is generally greatly reduced ...if the cellular substrates are fully differentiated cells. For example, in the nematode
, the ectopic expression of a neuronal identity-inducing transcription factor, CHE-1, can effectively induce CHE-1 target genes in immature cells but not in fully mature non-neuronal cells. To understand the molecular basis of this progressive restriction of cellular plasticity, we screened for
mutants in which ectopically expressed CHE-1 is able to induce neuronal effector genes in epidermal cells. We identified a ubiquitin hydrolase,
, that restricts cellular plasticity with a notable cellular specificity. Even though we find
to be very broadly expressed in all tissue types,
null mutants specifically make epidermal cells susceptible to CHE-1-mediated activation of neuronal target genes. We screened for additional genes that allow epidermal cells to be at least partially reprogrammed by ectopic
expression and identified many additional proteins that restrict cellular plasticity of epidermal cells, including a chromatin-related factor (H3K79 methyltransferase, DOT-1.1), a transcription factor (nuclear hormone receptor NHR-48), two MAPK-type protein kinases (SEK-1 and PMK-1), a nuclear localized O-GlcNAc transferase (OGT-1) and a member of large family of nuclear proteins related to the Rb-associated LIN-8 chromatin factor. These findings provide novel insights into the control of cellular plasticity.
The coverage-dependent mode of adsorption of terephthalic acid C6H4(COOH)2, TPA on rutile TiO2(110) was investigated by means of noncontact atomic force microscopy (NC-AFM) and near-edge X-ray ...absorption fine structure (NEXAFS) spectroscopy under ultrahigh vacuum conditions at room temperature. Individual molecules are observed to adsorb in an disordered, flat-lying geometry at low coverages up to ∼0.3 monolayer (ML). The molecules are immobile at room temperature, implying a diffusion barrier larger than 0.8 eV. This rather high value might be explained by anchoring to surface defect sites. A transition from flat-lying to upright-oriented molecules is revealed by NEXAFS when saturation coverage is achieved. High-resolution NC-AFM images reveal two different structures at coverages between ∼0.8 and 1 ML: (i) a well-ordered (2 × 1) structure and (ii) a structure of single and paired rows oriented along the 001 crystallographic direction. The latter structure might originate from a pairwise interaction of two neighboring molecules through the top carboxyl groups. Further increase in the exposure results in a saturation of the corresponding signal in the NEXAFS spectra, revealing that the growth of TPA on TiO2(110) at room temperature is self-limiting.
Nuclear spins of phosphorus P donor atoms in crystalline silicon are among the most coherent qubits found in nature. For their utilization in scalable quantum computers, distinct donor electron ...wavefunctions must be controlled and probed through electrical coupling by application of either highly localized electric fields or spin-selective currents. Due to the strong modulation of the P-donor wavefunction by the silicon lattice, such electrical coupling requires atomic spatial accuracy. Here, the spatially controlled application of electrical current through individual pairs of phosphorus donor electron states in crystalline silicon and silicon dangling bond states at the crystalline silicon (100) surface is demonstrated using a high-resolution scanning probe microscope operated under ultra-high vacuum and at a temperature of 4.3 K. The observed pairs of electron states display qualitatively reproducible current-voltage characteristics with a monotonous increase and intermediate current plateaus.
Precise
gene expression is crucial for embryonic patterning. Intra-
transcription factor binding and distal enhancer elements have emerged as the major regulatory modules controlling
gene expression. ...However, quantifying their relative contributions has remained elusive. Here, we introduce "synthetic regulatory reconstitution," a conceptual framework for studying gene regulation, and apply it to the
cluster. We synthesized and delivered variant rat
clusters (130 to 170 kilobases) to an ectopic location in the mouse genome. We found that a minimal
cluster recapitulated correct patterns of chromatin remodeling and transcription in response to patterning signals, whereas the addition of distal enhancers was needed for full transcriptional output. Synthetic regulatory reconstitution could provide a generalizable strategy for deciphering the regulatory logic of gene expression in complex genomes.
Modern republicanism - distinguished from its classical counterpart by its commercial character and jealous distrust of those in power, by its use of representative institutions, and by its ...employment of a separation of powers and a system of checks and balances - owes an immense debt to the republican experiment conducted in England between 1649, when Charles I was executed, and 1660, when Charles II was crowned. Though abortive, this experiment left a legacy in the political science articulated both by its champions, John Milton, Marchamont Nedham, and James Harrington, and by its sometime opponent and ultimate supporter, Thomas Hobbes. This volume examines these four thinkers, situates them with regard to the novel species of republicanism first championed in the early 1500s by Niccolò Machiavelli, and examines the debt that he and they owed the Epicurean tradition in philosophy and the political science crafted by the Arab philosophers Alfarabi, Avicenna, and Averroës.
The purpose of this study was to investigate the possible absence of teeth in the postcanine region of the upper jaw of the unoperated adult cleft patient.
The study was performed on 266 dental casts ...of fully unoperated adult cleft patients. The patients were divided into four groups according to the type of the cleft: unilateral cleft lip and alveolus, unilateral cleft lip and palate, bilateral cleft lip and alveolus, and bilateral cleft lip and palate.
No absence of permanent teeth in the canine and postcanine area of the upper jaw could be found.
The results are in contradiction with the established hypothesis that absence of teeth outside the cleft area of the maxilla is due to an unknown congenital factor. On the contrary, the findings support the hypothesis that surgery for the closure of the hard palate in early childhood is the most important etiological factor for the absence of teeth outside the cleft area in the early operated cleft patient. The superficial position of the tooth germs (at the time of the palatal surgery), especially those of the premolars, supports this hypothesis.
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