Ethyl and isopropyl 4-ferrocenylbenzoate.

The title compounds, [Fe(C5H5)(C14H13O2)] and [Fe(C5H5)- (C15H15O2)], respectively, contain the ferrocenyl 5(C5H4) and phenylene ±C6H4± rings in a nearly coplanar arrangement, with interplanar angles of 6.88 (12) and 10.5 (2), respectively. Molecules of the ethyl ester form dimers through 5(C5H5)CÐ H O C hydrogen bonds, with graph set R22 (20), and, together with Csp3ÐH (C5H5) interactions, generate a one-dimensional column (irregular ladder). Molecules of the isopropyl ester aggregate through 5(C5H5)CÐH (C6H4) interactions

Insulin direct pancreatic progenitor cell differentiation via Pdx1 regulation

poster abstractDifferentiation of early foregut endoderm into pancreatic endocrine and exocrine cells depends on a sequence of gene expression directed by various signals secreted from nearby tissue. Prior studies have shown that the pancreas is derived from Pdx1+ progenitor cells; however Pdx1 is turned off in pancreatic exocrine cells and α cells while maintained in β cells. Here, using zebrafish genetic knockdown, we showed that insulin secreted by early β cells can repress Pdx1 expression in pancreatic progenitor cells allowing them to differentiate to different pancreatic cell types. Knockdown of insulin gene severely impairs exocrine pancreas development. My results further demonstrate that inhibition of insulin signaling can induce pre-differentiation of Pdx1+ progenitor cells to β cells and Pdx1+ α cells. These Pdx1+ α cells can transdifferentiate to β cells following β cell ablation. Overall, these data represent the first in vivo evidence of local insulin signaling on pancreas development via regulation of Pdx1 expression

Replication stress and chromatin context link ATM activation to a role in DNA replication

ATM-mediated signaling in response to DNA damage is a barrier to tumorigenesis. Here we asked whether replication stress could also contribute to ATM signaling. We demonstrate that, in the absence of DNA damage, ATM responds to replication stress in a hypoxia-induced heterochromatin-like context. In certain hypoxic conditions, replication stress occurs in the absence of detectable DNA damage. Hypoxia also induces H3K9me3, a histone modification associated with gene repression and heterochromatin. Hypoxia-induced replication stress together with increased H3K9me3 leads to ATM activation. Importantly, ATM prevents the accumulation of DNA damage in hypoxia. Most significantly, we describe a stress-specific role for ATM in maintaining DNA replication rates in a background of increased H3K9me3. Furthermore, the ATM-mediated response to oncogene-induced replication stress is enhanced in hypoxic conditions. Together, these data indicate that hypoxia plays a critical role in the activation of the DNA damage response, therefore contributing to this barrier to tumorigenesis

The Principle of Symmetric Criticality in General Relativity

We consider a version of Palais' Principle of Symmetric Criticality (PSC) that is applicable to the Lie symmetry reduction of Lagrangian field theories. PSC asserts that, given a group action, for any group-invariant Lagrangian the equations obtained by restriction of Euler-Lagrange equations to group-invariant fields are equivalent to the Euler-Lagrange equations of a canonically defined, symmetry-reduced Lagrangian. We investigate the validity of PSC for local gravitational theories built from a metric. It is shown that there are two independent conditions which must be satisfied for PSC to be valid. One of these conditions, obtained previously in the context of transverse symmetry group actions, provides a generalization of the well-known unimodularity condition that arises in spatially homogeneous cosmological models. The other condition seems to be new. The conditions that determine the validity of PSC are equivalent to pointwise conditions on the group action alone. These results are illustrated with a variety of examples from general relativity. It is straightforward to generalize all of our results to any relativistic field theory.Comment: 46 pages, Plain TeX, references added in revised versio

OpTiDDM (Optical Tweezers integrating Differential Dynamic Microscopy) maps the spatiotemporal propagation of nonlinear stresses in polymer blends and composites

How local stresses propagate through polymeric fluids, and, more generally, how macromolecular dynamics give rise to viscoelasticity are open questions vital to wide-ranging scientific and industrial fields. Here, to unambiguously connect polymer dynamics to force response, and map stress propagation in macromolecular materials, we present a powerful approach-Optical Tweezers integrating Differential Dynamic Microscopy (OpTiDMM)-that simultaneously imposes local strains, measures resistive forces, and analyzes the motion of the surrounding polymers. Our measurements with blends of ring and linear polymers (DNA) and their composites with stiff polymers (microtubules) uncover a surprising resonant response, in which affine alignment, superdiffusivity, and elastic memory are maximized when the strain rate is comparable to the entanglement rate. Microtubules suppress this resonance, while substantially increasing elastic force and memory, due to varying degrees to which the polymers buildup, stretch and flow along the strain path, and configurationally dissipate stress. More broadly, the rich multi-scale coupling of mechanics and dynamics afforded by OpTiDDM, empowers its interdisciplinary use to elucidate non-trivial phenomena that sculpt stress propagation dynamics-critical to commercial applications and cell mechanics alike.Comment: 32 pages, 10 figure

Polymer threadings and rigidity dictate the viscoelasticity and nonlinear relaxation dynamics of entangled ring-linear blends and their composites with rigid rod microtubules

Mixtures of polymers of varying topologies and stiffnesses display complex emergent rheological properties that often cannot be predicted from their single-component counterparts. For example, entangled blends of ring and linear polymers have been shown to exhibit enhanced shear thinning and viscosity, as well as prolonged relaxation timescales, compared to pure solutions of rings or linear chains. These emergent properties arise in part from the synergistic threading of rings by linear polymers. Topology has also been shown to play an important role in composites of flexible (e.g., DNA) and stiff (e.g., microtubules) polymers, whereby rings promote mixing while linear polymers induce de-mixing and flocculation of stiff polymers, with these topology-dependent interactions giving rise to highly distinct rheological signatures. To shed light on these intriguing phenomena, we use optical tweezers microrheology to measure the linear and nonlinear rheological properties of entangled ring-linear DNA blends and their composites with rigid microtubules. We show that the linear viscoelasticity is primarily dictated by the microtubules at lower frequencies, but their contributions become frozen out at frequencies above the DNA entanglement rate. In the nonlinear regime, we reveal that mechanical response features, such as shear thinning, stress softening and multi-modal relaxation dynamics are mediated by entropic stretching, threading, and flow alignment of entangled DNA, as well as forced de-threading, disentanglement, and clustering. The contributions of each of these mechanisms depend on the strain rate as well as the entanglement density and stiffness of the polymers, leading to non-monotonic rate dependences of mechanical properties that are most pronounced for highly concentrated ring-linear blends rather than DNA-MT composites.Comment: 22 pages, 8 figure

The Intergenerational Transmission of Automobile Brand Preferences

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116373/1/joie12092.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/116373/2/joie12092-sup-0001-si.pd

An insulin signaling feedback loop regulates pancreas progenitor cell differentiation during islet development and regeneration

As one of the key nutrient sensors, insulin signaling plays an important role in integrating environmental energy cues with organism growth. In adult organisms, relative insufficiency of insulin signaling induces compensatory expansion of insulin-secreting pancreatic beta (β) cells. However, little is known about how insulin signaling feedback might influence neogenesis of β cells during embryonic development. Using genetic approaches and a unique cell transplantation system in developing zebrafish, we have uncovered a novel role for insulin signaling in the negative regulation of pancreatic progenitor cell differentiation. Blocking insulin signaling in the pancreatic progenitors hastened the expression of the essential β cell genes insulin and pdx1, and promoted β cell fate at the expense of alpha cell fate. In addition, loss of insulin signaling promoted β cell regeneration and destabilization of alpha cell character. These data indicate that insulin signaling constitutes a tunable mechanism for β cell compensatory plasticity during early development. Moreover, using a novel blastomere-to-larva transplantation strategy, we found that loss of insulin signaling in endoderm-committed blastomeres drove their differentiation into β cells. Furthermore, the extent of this differentiation was dependent on the function of the β cell mass in the host. Altogether, our results indicate that modulation of insulin signaling will be crucial for the development of β cell restoration therapies for diabetics; further clarification of the mechanisms of insulin signaling in β cell progenitors will reveal therapeutic targets for both in vivo and in vitro β cell generation