A dynamic role for transcription factors in restoring transcription through mitosis.

Mitosis involves intricate steps, such as DNA condensation, nuclear membrane disassembly, and phosphorylation cascades that temporarily halt gene transcription. Despite this disruption, daughter cells remarkably retain the parent cell's gene expression pattern, allowing for efficient transcriptional memory after division. Early studies in mammalian cells suggested that transcription factors (TFs) mark genes for swift reactivation, a phenomenon termed 'mitotic bookmarking', but conflicting data emerged regarding TF presence on mitotic chromosomes. Recent advancements in live-cell imaging and fixation-free genomics challenge the conventional belief in universal formaldehyde fixation, revealing dynamic TF interactions during mitosis. Here, we review recent studies that provide examples of at least four modes of TF-DNA interaction during mitosis and the molecular mechanisms that govern these interactions. Additionally, we explore the impact of these interactions on transcription initiation post-mitosis. Taken together, these recent studies call for a paradigm shift toward a dynamic model of TF behavior during mitosis, underscoring the need for incorporating dynamics in mechanistic models for re-establishing transcription post-mitosis.

Structural Properties of Some Vacancy-Ordered Platinum Halide Perovskites.

The structural changes that accompany the dehydration of Na2PtX6·6H2O (X = Cl, Br) were studied using in situ variable temperature synchrotron X-ray diffraction. The two hexahydrates are isostructural, containing isolated PtX6 octahedra separated by Na cations. Removal of the water results in the formation of the anhydrous vacancy ordered double perovskites Na2PtX6. The Na cation is too small for the cuboctahedron site of the parent cubic structure, resulting in cooperative tilting of the PtX6 octahedra and lowering of the symmetry. Replacing Na with a larger alkali metal (K, Rb, or Cs) invariably enabled the isolation of the anhydrous hexahalide, and we found no evidence that these readily hydrated. For all cations, other than Na, it was possible to observe the archetypical cubic structure, although for the two potassium salts K2PtBr6 and K2PtI6, this was only observed above a critical temperature of 175 and 460 K, respectively. As these two samples were cooled, symmetry lowering was observed, yielding a tetragonal structure initially and ultimately a monoclinic structure: Fm3̅m → P4/mnc → P21/n. These phase transitions are associated with the onset of long-range cooperative tilting of the PtX6 octahedra described using the Glazer tilt notation as a0a0a0 → a0a0c+ → a-a-c+.

Structural and Magnetic Studies of ABO4-Type Ruthenium and Osmium Oxides.

Oxides of the form ABO4 with A = K, Rb, Cs and B = Ru and Os have been synthesized and characterized by diffraction and magnetic techniques. For A = K the oxides adopted the tetragonal (I41/a) scheelite structure. RbOsO4, which crystallizes as a scheelite at room temperature, underwent a continuous phase transition to I41/amd near 550 K. RbRuO4 and CsOsO4 were found to crystallize in the orthorhombic (Pnma) pseudoscheelite structure, and both displayed discontinuous phase transitions to I41/a at high temperatures. CsOsO4 was determined to undergo a phase transition to a P21/c structure below 140 K. CsRuO4 crystallizes with a baryte-type structure at room temperature. Upon heating CsRuO4 a first order phase transition to the scheelite structure in I41/a is observed at 400 K. A continuous phase transition is observed to P212121 below 140 K. DC magnetic susceptibility data is consistent with long-range antiferromagnetic ordering at low temperatures for all compounds except for CsOsO4, which is paramagnetic to 2 K. The effective magnetic moments are in agreement with the spin only values for an S = 1/2 quantum magnet. Effective magnetic moments calculated for Os compounds were lower than their Ru counterparts, reflective of an enhanced spin orbit coupling effect. A magnetic structure is proposed for RbRuO4 consisting of predominately antiferromagnetic (AFM) ordering along the 001 direction, with canting of spins in the 100 plane. A small ordered magnetic moment of 0.77 µB was determined.

Hydrothermal Liquefaction of α-O-4 Aryl Ether Linkages in Lignin.

By using lignin model compounds with relevant key characteristic structural features, the reaction pathways of α-O-4 aryl ether linkages under hydrothermal conditions are elucidated. Experimental results and computational modeling suggest that the α-O-4 linkages in lignin undergo catalyzed hydrolysis and elimination to give phenolic and alkenylbenzene derivatives as major products in subcritical water. The decreased relative permittivity of water at these high temperatures and pressures facilitates the elimination reactions. The alkyl group on the α-carbon and the methoxy groups on the phenyl rings both have positive effects on the rate of conversion of α-O-4 linkages in native lignin.

The target uric acid level in multimorbid patients with gout is difficult to achieve: data from a longitudinal Swiss single-centre cohort.

OBJECTIVE: To characterise adherence and treat-to-target (T2T) strategy in gout patients within a Swiss tertiary hospital. METHODS: Consecutive presenting patients with proven gout were prospectively included in this cohort. Symptoms, comorbidities, medication and laboratory values were assessed (during hospitalisation and at planned 3- and 12-month follow-up assessments). RESULTS: 116 patients (98 men) with a mean age of 67 (range 23–94 years) were included, 74% of whom had active arthritis. Comorbidities were frequent: hypertension, renal impairment, and obesity were present in 72, 55 and 35% of patients, respectively. Thirty-five percent of patients received urate-lowering treatment at inclusion. Only 62 and 50% attended the 3- and 12-month follow-up. The target serum uric acid level of <360 μmol/l was achieved in 22 and 57% of patients by the 3- and 12-month follow-up visits, respectively. Patients followed up by rheumatologists reached the target serum uric acid at follow-up more often than those that were not (p = 0.033). Median daily allopurinol dose at 12-month follow-up was 300 mg in those achieving T2T and 100 mg in the others (p = 0.033). Flares occurred during the first 3 months in 52% and during the subsequent 9 months in 47% of patients. CONCLUSION: Only half of patients attended the planned follow-up visits, indicating low awareness for gout. Of those attending follow-up, only approximately 50% had achieved the serum urate target at 12 months. Although new treatments are available, care for gout patients remains insufficient, notably in difficult-to-treat multimorbid patient subsets as described in this cohort.

Structural and magnetic studies of KOsO4, a 5d1 quantum magnet oxide.

The quantum magnet KOsO4 has been characterized by a combination of X-ray and neutron diffraction techniques. The tetrahedrally coordinated Os7+ 5d1S = 1/2 cations were determined to order antiferromagnetically along the c axis below 35 K. A miniscule ordered magnetic moment of 0.46(18) µB was determined per Os7+ cation.

Unravelling Some of the Key Transformations in the Hydrothermal Liquefaction of Lignin.

Using both experimental and computational methods, focusing on intermediates and model compounds, some of the main features of the reaction mechanisms that operate during the hydrothermal processing of lignin were elucidated. Key reaction pathways and their connection to different structural features of lignin were proposed. Under neutral conditions, subcritical water was demonstrated to act as a bifunctional acid/base catalyst for the dissection of lignin structures. In a complex web of mutually dependent interactions, guaiacyl units within lignin were shown to significantly affect overall lignin reactivity.

Masked N-Heterocyclic Carbene-Catalyzed Alkylation of Phenols with Organic Carbonates.

An easily prepared masked N-heterocyclic carbene, 1,3-dimethylimidazolium-2-carboxylate (DMI-CO2 ), was investigated as a "green" and inexpensive organocatalyst for the alkylation of phenols. The process made use of various low-toxicity and renewable alkylating agents, such as dimethyl- and diethyl carbonate, in a focused microwave reactor. DMI-CO2 was found to be a very active catalyst and excellent yields of a range of aryl alkyl ethers were obtained under relatively benign conditions. The observed difference in the conversion behavior of phenol methylation, in the presence of either the carbene or 1,8-diazabicycloundec-7-ene (DBU) catalyst, was rationalized on the basis of mechanistic investigations. The primary mode of action for the N-heterocyclic carbene is nucleophilic catalysis. Activation of the dialkyl carbonate electrophile results in concomitant evolution of an organo-soluble alkoxide, which deprotonates the phenolic starting material. In contrast, DBU is initially protonated by the phenol and thus consumed. Subsequent regeneration and participation in nucleophilic catalysis only becomes significant after some phenolate alkylation occurs.

Ionic liquids are compatible with on-water catalysis.

A major limitation of on-water catalysis has been the need for liquid reactants to enable emulsification. We demonstrate that ionic liquids are compatible with on-water catalysis, enabling on-water catalysed reactions for otherwise unreactive solid-solid systems. The unique solvation properties of ionic liquids dramatically expands the scope of on-water catalysis.

A flexible, bolaamphiphilic template for mesoporous silicas.

A novel symmetrical bolaamphiphile, containing two N-methylimidazolium head-groups bridged by a 32-methylene linker, was synthesized and characterized. A variety of mesoporous silicas was prepared using the bolaamphiphile as a "soft template". The effects of absolute surfactant concentration and synthesis conditions upon the morphologies of these silicas were investigated. For a given surfactant concentration, particle morphology; pore size; and pore ordering were modified through control of the template to silica-precursor ratio and synthesis conditions. Observed morphologies included: lenticular core-shell nanoparticles and decorticated globules, truncated hexagonal plates, and sheets. In all cases the mesopores are aligned along the shortest axis of the nanomaterial. Decorticated materials displayed surface areas of up to 1200 m(2) g(-1) and pore diameters (D(BJH)) of 24-28 Å. Small-angle X-ray diffraction and transmission electron microscopy measurements revealed that the majority of the materials has elliptical pores arranged in rectangular lattices (c2mm). Adoption of this symmetry group is a result of the template aggregate deformation from a regular hexagonal phase of cylindrical rods to a ribbon phase under the synthetic conditions.

The role of the reactor wall in hydrothermal biomass conversions.

The processing of renewable feedstocks to platform chemicals and, to a lesser degree, fuels is a key part of sustainable development. In particular, the combination of lignocellulosic biomass with hydrothermal upgrading (HTU), using high temperature and pressure water (HTPW), is experiencing a renaissance. One of the many steps in this complicated process is the in-situ hydrogenation of intermediate compounds. As formic acid and related low-molecular-weight oxygenates are among the species generated, it is conceivable that they act as a hydrogen source. Such hydrogenations have been suggested to be catalyzed by water, by bases like NaOH, and/or to involve "reactive/nascent hydrogen". To achieve the temperatures and pressures required for HTU, it is necessary to conduct the reactions in high-pressure vessels. Metals are typical components of their walls and/or internal fittings. Here, using cyclohexanone as a model compound for more complex biomass-derived molecules, iron in the wall of high-pressure stainless steel reactors is shown to be responsible for the hydrogenation of ketones with low-molecular-weight oxygenates acting as a hydrogen source in combination with water.

Exploring the myth of nascent hydrogen and its implications for biomass conversions.

Iron (and to a lesser extent manganese) in the wall of a 316 stainless steel (SS) reactor is responsible for the hydrogenation of cyclohexanone to cyclohexanol when using an aqueous formic acid solution under high temperature and pressure water (HTPW) conditions. However, not only dilute formic acid but also aqueous solutions of several other organic and mineral acids in the presence of iron are active in this reaction covering a range of aldehydes and ketones, even under ambient conditions. The stoichiometry, kinetics, and the possible mechanisms of both dihydrogen production as well as of the hydrogenation of the model compound cyclohexanone were examined. The reduction is essentially stoichiometric with respect to metallic iron, and the conversions are highly dependent on the speed of stirring as well as temperature and reactant concentrations. Importantly, it is established unequivocally that water participates in dihydrogen gas formation (hydrogen atoms originate from both the acid and water molecules) and facilitates substrate reduction.

The interplay of catechol ligands with nanoparticulate iron oxides.

The unique properties exhibited by nanoscale materials, coupled with the multitude of chemical surface derivatisation possibilities, enable the rational design of multifunctional nanoscopic devices. Such functional devices offer exciting new opportunities in medical research and much effort is currently invested in the area of "nanomedicine", including: multimodal imaging diagnostic tools, platforms for drug delivery and vectorisation, polyvalent, multicomponent vaccines, and composite devices for "theranostics". Here we will review the surface derivatisation of nanoparticulate oxides of iron and iron@iron-oxide core-shells. They are attractive candidates for MRI-active therapeutic platforms, being potentially less toxic than lanthanide-based materials, and amenable to functionalisation with ligands. However successful grafting of groups onto the surface of iron-based nanoparticles, thus adding functionality whilst preserving their inherent properties, is one of the most difficult challenges for creating truly useful nanodevices from them. Functionalised catechol-derived ligands have enjoyed success as agents for the masking of superparamagnetic iron-oxide particles, often so as to render them biocompatible with medium to long-term colloidal stability in the complex chemical environments of biological milieux. In this perspective, the opportunities and limitations of functionalising the surfaces of iron-oxide nanoparticles, using coatings containing a catechol-derived anchor, are analysed and discussed, including recent advances using dopamine-terminated stabilising ligands. If light-driven ligand to metal charge transfer (LMCT) processes, and pH-dependent ligand desorption, leading to nanoparticle degradation under physiologically relevant conditions can be suppressed, colloidal stability of samples can be maintained and toxicity ascribed to degradation products avoided. Modulation of the redox behaviour of iron catecholate systems through the introduction of an electron-withdrawing substituent to the aromatic π-system of the catechol is a promising approach towards achieving these goals.

Measurement of long-range interatomic distances by solid-state tritium-NMR spectroscopy.

For the structural determination of a ligand bound to an amorphous macromolecular system, solid-state NMR can be used to provide interatomic distances. It is shown here that selective labeling in discrete locations with tritium enables accurate measurement of long-range distances owing to the high gyromagnetic ratio of this nucleus, without structural modification of the molecule. This approach gives access to the largest NMR distance ever measured between two nuclei (14.4 A). (3)H MAS NMR appears to be a promising tool for structural applications in the biological and material sciences.

Role of physical exercise in low back pain rehabilitation: a randomized controlled trial of a three-month exercise program in patients who have completed multidisciplinary rehabilitation.

STUDY DESIGN: Randomized controlled trial with 1-year follow-up. OBJECTIVE: To analyze the effects of an exercise program or routine follow-up on patients with chronic low back pain who have completed functional multidisciplinary rehabilitation. The short- and long-term outcome in terms of symptoms and physical and social functioning was compared. SUMMARY OF BACKGROUND DATA: Systematic reviews have shown that functional multidisciplinary rehabilitation improves physical function and reduces pain in patients with chronic low back pain. However, long-term maintenance of these improvements is inconsistent and the role of exercise in achieving this goal is unclear. METHODS: One hundred five chronic patients with low back pain who had completed a 3-week functional multidisciplinary rehabilitation program were randomized to either a 3-month exercise program (n = 56) or routine follow-up (n = 49). The exercise program consisted of 24 training sessions during 12 weeks. Patients underwent evaluations of trunk muscle endurance, cardiovascular endurance, lumbar spine mobility (flexion and extension range-of-motion, fingertip-to-floor distance), pain and perceived functional ability at the beginning and the end of functional multidisciplinary rehabilitation, at the end of the exercise program (3 months) and at 1-year follow-up. Disability was also assessed at the same time points except at the beginning of functional multidisciplinary rehabilitation. RESULTS: At the end of the functional multidisciplinary rehabilitation, both groups improved significantly in all physical parameters except flexion and extension range-of-motion. At the 3 month and 1 year follow-up, both groups maintained improvements in all parameters except for cardiovascular endurance. Only the exercise program group improved in disability score and trunk muscle endurance. No differences between groups were found. CONCLUSION: A favorable long-term outcome was observed after functional multidisciplinary rehabilitation in both patient groups. Patients who participated in an exercise program obtained some additional benefits. The relevance of these benefits to overall health status need to be further investigated.

Short-term efficacy of intravenous pulse glucocorticoids in acute discogenic sciatica. A randomized controlled trial.

STUDY DESIGN: Double-blinded randomized controlled trial. OBJECTIVE: To test the short-term efficacy of a single intravenous (IV) pulse of glucocorticoids on the symptoms of acute discogenic sciatica. SUMMARY OF BACKGROUND DATA: The use of glucocorticoids in the treatment of acute discogenic sciatica is controversial. A potential advantage of the IV pulse therapy is the ability to distribute high glucocorticoid concentrations to the area surrounding the prolapsed disc without the risks and inconveniences of an epidural injection. METHODS: Patients with acute sciatica (<6-week duration) of radiologically confirmed discogenic origin were randomized to receive either a single IV bolus of 500 mg of methylprednisolone or placebo. Clinical evaluation was performed in a double-blind manner on days 0, 1, 2, 3, 10, and 30. The primary outcome was reduction in sciatic leg pain during the first 3 days following the infusion; secondary outcomes were reduction in low back pain, global pain, functional disability, and signs of radicular irritation. The analysis was performed on an intent-to-treat basis using a longitudinal regression model for repeated measures. RESULTS: A total of 65 patients were randomized, and 60 completed the treatment and the follow-up assessments. A single IV bolus of glucocorticoids provided significant improvement in sciatic leg pain (P = 0.04) within the first 3 days. However, the effect size was small, and the improvement did not persist. IV glucocorticoids had no effect on functional disability or clinical signs of radicular irritation. CONCLUSIONS: Although an IV bolus of glucocorticoids provides a short-term improvement in leg pain in patients with acute discogenic sciatica, its effects are transient and have small magnitude.

Spectacle-mounted prisms as an aid in face-down positioning after vitrectomy surgery.

PURPOSE: To report a modification in the design of bed spectacles to provide an aid for patients who undergo face-down positioning after vitrectomy with gas-fluid exchange and postoperative gas tamponade. METHODS: New equipment design. Bed spectacles that use prisms to move the image 90 degrees around the horizontal meridian were modified by rotating the prisms in the frame 180 degrees and adding nosepads and cable temples. The spectacles were given to 12 patients for use during postoperative face-down positioning. A questionnaire was used to evaluate the helpfulness of the spectacles during face-down positioning. RESULTS: Patients ranked the spectacles as "helpful" to "very helpful" with a mean and SD of 8.3+/-1.6 on a scale of 1 to 10, where 1 was "a hindrance" and 10 was "very helpful." Patients wore the spectacles an average of 5.7+/-4.5 hours a day (range, 1.5 to 15 hours). CONCLUSION: Modified bed spectacles appear to be a portable aid to patients who undergo face-down positioning while sitting, standing, or prone.

First-grade classroom behavior: its short- and long-term consequences for school performance.

Effects of children's classroom behavior on school performance over a 4-year period are examined for a large, representative panel of beginning first graders. Scales developed from homeroom teachers' ratings of children in the spring of their first, second, and fourth years of school are used to predict spring marks in reading and math and spring scores on verbal and quantitative subtests from the CAT battery. The teachers' ratings cluster in three domains: Interest-Participation (I-P), Cooperation-Compliance (C-C), and Attention Span-Restlessness (A-R). The I-P and A-R ratings, but not C-C ratings, affect test score gains in first grade and marks in all 3 years. Behavior ratings from Year 1 also affect Year 2 and Year 4 performance, with indications that effects are understated over single-year periods. The importance of assessing classroom behavior in a longitudinal framework that allows for lagged and cumulative effects is discussed.

Detection of antibody responses and delayed dermal hypersensitivity with Blastomyces dermatitidis yeast and mycelial lysate antigens.

Yeast cell lysate and mycelial lysate antigens prepared from one strain (T-58) of Blastomyces dermatitidis were evaluated with respect to the detection of antibodies and delayed dermal hypersensitivity. Comparable ELISA sensitivity values were evidenced with the two antigens when assayed against serum specimens from dogs with blastomycosis, sera from non-infected dogs residing in endemic and non-endemic areas for blastomycosis and sera from rabbits that were hyperimmunized with B. dermatitidis antigens. Specificity determinations with anti-Histoplasma capsulatum rabbit sera indicated that both reagents exhibited only minimal cross-reactivity; the mycelial antigen was slightly more specific than the yeast phase reagent. Similar sensitivity and specificity results were experienced when the two antigens were used to detect delayed dermal hypersensitivity in guinea pigs previously sensitized with B. dermatitidis or H. capsulatum.

Beginning school math competence: minority and majority comparisons.

This article uses a structural model with a large random sample of urban children to explain children's competence in math concepts and computation at the time they begin first grade. These 2 aspects of math ability respond differently to environmental resources, with math concepts (reasoning) much more responsive to family factors before formal schooling begins than is computation. In this sample, blacks and whites are equivalent in terms of computational and verbal skills as measured by the California Achievement Test at the start of grade 1. However, there is a significant difference of about a quarter of a standard deviation favoring whites over blacks in terms of math concepts (reasoning skills). Both black and white children of all socioeconomic levels respond to parents' psychological resources: net of ability or other factors, children score higher if parents expect them to do well. Socioeconomic resources in the home also help both groups. In particular, the parent being a high school graduate as opposed to a dropout is important. When parents' material and psychological resources are taken into account, family configuration (solo motherhood vs. other types) has no discernible effects on either type of math performance.