MYB regulates the SUMO protease SENP1 and its novel interaction partner UXT, modulating MYB target genes and the SUMO landscape.

SUMOylation is a post-translational modification frequently found on nuclear proteins, including transcription factors (TFs) and coactivators. By controlling the activity of several TFs, SUMOylation may have far-reaching effects. MYB is an example of a developmental TF subjected to SUMO-mediated regulation, through both SUMO conjugation and SUMO binding. How SUMO affects MYB target genes is unknown. Here, we explored the global effect of reduced SUMOylation of MYB on its downstream gene programs. RNA-Seq in K562 cells after MYB knockdown and rescue with mutants having an altered SUMO status revealed a number of differentially regulated genes and distinct gene ontology term enrichments. Clearly, the SUMO status of MYB both quantitatively and qualitatively affects its regulome. The transcriptome data further revealed that MYB upregulates the SUMO protease SENP1, a key enzyme that removes SUMO conjugation from SUMOylated proteins. Given this role of SENP1 in the MYB regulome, we expanded the analysis, mapped interaction partners of SENP1, and identified UXT as a novel player affecting the SUMO system by acting as a repressor of SENP1. MYB inhibits the expression of UXT suggesting that MYB is able not only to control a specific gene program directly but also indirectly by affecting the SUMO landscape through SENP1 and UXT. These findings suggest an autoactivation loop whereby MYB, through enhancing SENP1 and reducing UXT, is itself being activated by a reduced level of repressive SUMOylation. We propose that overexpressed MYB, seen in multiple cancers, may drive this autoactivation loop and contribute to oncogenic activation of MYB.

Predictive factors of post-HoLEP incontinence: differences between stress and urgency urinary incontinence.

INTRODUCTION: The analysis of post-HoLEP urinary incontinence (UI) has traditionally focused on stress UI. Our aim is to evaluate the factors associated with stress and urgency UI in the first month after the surgery. METHODS: Data were obtained from patients who underwent HoLEP by the same experienced surgeon. UI was evaluated at one month and at 6 months after the surgery. Three groups were defined: continent patients, patients with pure urgency UI and patients with stress or mixed UI. Preoperative, intraoperative, urodynamic and clinical variables were analyzed and compared between the three groups. RESULTS: In total, 235 subjects were included. One month after the surgery, 156 (66.5%) were continent (group 1), 49 (20.8%) reported pure urgency UI (group 2), and 30 (12.7%) reported some level of stress UI (group 3). In Group 2, the factors associated with urgency UI in the univariate analysis were age, presurgical urgency UI, having diabetes or hypertension. In Group 3, age, prostatic volume, preoperative PSA, time of enucleation, weight of the resection in grams, having an IDC or being diabetic were significant in the univariate analysis. In the multivariate analysis, age predicts both types of UI, while prostatic volume and having an IDC predict stress or mixed UI. CONCLUSION: In the first month post-HoLEP, age is a predictive factor of urgency UI and stress UI. In addition, prostatic volume and the presence of an indwelling urinary catheter are predictive factors of stress UI.

The SUMO protease SENP1 and the chromatin remodeler CHD3 interact and jointly affect chromatin accessibility and gene expression.

The small ubiquitin-like modifier (SUMO) post-translationally modifies lysine residues of transcription factors and co-regulators and thereby contributes to an important layer of control of the activities of these transcriptional regulators. Likewise, deSUMOylation of these factors by the sentrin-specific proteases (SENPs) also plays a role in gene regulation, but whether SENPs functionally interact with other regulatory factors that control gene expression is unclear. In the present work, we focused on SENP1, specifically, on its role in activation of gene expression investigated through analysis of the SENP1 interactome, which revealed that SENP1 physically interacts with the chromatin remodeler chromodomain helicase DNA-binding protein 3 (CHD3). Using several additional methods, including GST pulldown and co-immunoprecipitation assays, we validated and mapped this interaction, and using CRISPR-Cas9-generated CHD3- and SENP1-KO cells (in the haploid HAP1 cell line), we investigated whether these two proteins are functionally linked in regulating chromatin remodeling and gene expression. Genome-wide ATAC-Seq analysis of the CHD3- and SENP1-KO cells revealed a large degree of overlap in differential chromatin openness between these two mutant cell lines. Moreover, motif analysis and comparison with ChIP-Seq profiles in K562 cells pointed to an association of CHD3 and SENP1 with CCCTC-binding factor (CTCF) and SUMOylated chromatin-associated factors. Lastly, genome-wide RNA-Seq also indicated that these two proteins co-regulate the expression of several genes. We propose that the functional link between chromatin remodeling by CHD3 and deSUMOylation by SENP1 uncovered here provides another level of control of gene expression.

Chromosome segregation in Archaea mediated by a hybrid DNA partition machine.

Eukarya and, more recently, some bacteria have been shown to rely on a cytoskeleton-based apparatus to drive chromosome segregation. In contrast, the factors and mechanisms underpinning this fundamental process are underexplored in archaea, the third domain of life. Here we establish that the archaeon Sulfolobus solfataricus harbors a hybrid segrosome consisting of two interacting proteins, SegA and SegB, that play a key role in genome segregation in this organism. SegA is an ortholog of bacterial, Walker-type ParA proteins, whereas SegB is an archaea-specific factor lacking sequence identity to either eukaryotic or bacterial proteins, but sharing homology with a cluster of uncharacterized factors conserved in both crenarchaea and euryarchaea, the two major archaeal sub-phyla. We show that SegA is an ATPase that polymerizes in vitro and that SegB is a site-specific DNA-binding protein contacting palindromic sequences located upstream of the segAB cassette. SegB interacts with SegA in the presence of nucleotides and dramatically affects its polymerization dynamics. Our data demonstrate that SegB strongly stimulates SegA polymerization, possibly by promoting SegA nucleation and accelerating polymer growth. Increased expression levels of segAB resulted in severe growth and chromosome segregation defects, including formation of anucleate cells, compact nucleoids confined to one half of the cell compartment and fragmented nucleoids. The overall picture emerging from our findings indicates that the SegAB complex fulfills a crucial function in chromosome segregation and is the prototype of a DNA partition machine widespread across archaea.

Modular architecture of Munc13/calmodulin complexes: dual regulation by Ca2+ and possible function in short-term synaptic plasticity.

Ca(2+) signalling in neurons through calmodulin (CaM) has a prominent function in regulating synaptic vesicle trafficking, transport, and fusion. Importantly, Ca(2+)-CaM binds a conserved region in the priming proteins Munc13-1 and ubMunc13-2 and thus regulates synaptic neurotransmitter release in neurons in response to residual Ca(2+) signals. We solved the structure of Ca(2+)(4)-CaM in complex with the CaM-binding domain of Munc13-1, which features a novel 1-5-8-26 CaM-binding motif with two separated mobile structural modules, each involving a CaM domain. Photoaffinity labelling data reveal the same modular architecture in the complex with the ubMunc13-2 isoform. The N-module can be dissociated with EGTA to form the half-loaded Munc13/Ca(2+)(2)-CaM complex. The Ca(2+) regulation of these Munc13 isoforms can therefore be explained by the modular nature of the Munc13/Ca(2+)-CaM interactions, where the C-module provides a high-affinity interaction activated at nanomolar [Ca(2+)](i), whereas the N-module acts as a sensor at micromolar [Ca(2+)](i). This Ca(2+)/CaM-binding mode of Munc13 likely constitutes a key molecular correlate of the characteristic Ca(2+)-dependent modulation of short-term synaptic plasticity.

Holmium laser enucleation of the prostate (HoLEP) in short-circuit outpatient care: Is prostatic volume a limiting factor?

INTRODUCTION AND OBJECTIVES: Our goals were to study prostatic volume as a limiting factor after HoLEP surgery with short-circuit outpatient care (4 h) and to define other factors that affect the success of the proposed circuit. MATERIALS AND METHODS: An observational analysis and review was performed using a prospective database. Preoperative, intraoperative, and postoperative variables were included for patients who were scheduled for short-circuit outpatient care (SCOC) and who underwent HoLEP between 2020 and 2023. We defined SCOC as a postoperative hospital stay of 4 h. Subjects who required more than 4 h in hospital were categorized as conventional hospital admission (CHA). A descriptive populational study was conducted, expressing the mean using a 95% confidence interval and percentages for the continuous variables. In order to analyze them, we used the Student's t-test for the continuous variables and the chi-squared test for the categorical variables. RESULTS: Sixty-eight patients were included, 54 of which completed SCOC, which represented a success ratio of 79.5%. The mean age and prostatic volume of the whole cohort were 68.9 (±6.8) years and 79.5 (±29.1) mL, respectively. We found no significant differences in age, prostatic volume, antiplatelet drug use, indwelling bladder catheter, or applied energy among the subjects who completed SCOC and those who required CHA. No patient was presented with a complication of Grade 3 (or higher) in the modified Clavien-Dindo classification. At the six-month follow-up, no differences were observed in the uroflowmetry or International Prostate Symptoms Score variables. CONCLUSIONS: Prostatic volume does not seem to be a limiting factor after undergoing HoLEP with short-circuit outpatient care.

Uncoupling of nucleotide hydrolysis and polymerization in the ParA protein superfamily disrupts DNA segregation dynamics.

DNA segregation in bacteria is mediated most frequently by proteins of the ParA superfamily that transport DNA molecules attached via the segrosome nucleoprotein complex. Segregation is governed by a cycle of ATP-induced polymerization and subsequent depolymerization of the ParA factor. Here, we establish that hyperactive ATPase variants of the ParA homolog ParF display altered segrosome dynamics that block accurate DNA segregation. An arginine finger-like motif in the ParG centromere-binding factor augments ParF ATPase activity but is ineffective in stimulating nucleotide hydrolysis by the hyperactive proteins. Moreover, whereas polymerization of wild-type ParF is accelerated by ATP and inhibited by ADP, filamentation of the mutated proteins is blocked indiscriminately by nucleotides. The mutations affect a triplet of conserved residues that are situated neither in canonical nucleotide binding and hydrolysis motifs in the ParF tertiary structure nor at interfaces implicated in ParF polymerization. Instead the residues are involved in shaping the contours of the binding pocket so that nucleotide binding locks the mutant proteins into a configuration that is refractory to polymerization. Thus, the architecture of the pocket not only is crucial for optimal ATPase kinetics but also plays a key role in the polymerization dynamics of ParA proteins that drive DNA segregation ubiquitously in procaryotes.

Epidemiology, Diagnosis and Management of Penile Cancer: Results from the Spanish National Registry of Penile Cancer.

INTRODUCTION: Penile cancer (PC) is a rare malignancy with an overall incidence in Europe of 1/100,000 males/year. In Europe, few studies report the epidemiology, risk factors, clinical presentation, and treatment of PC. The aim of this study is to present an updated outlook on the aforementioned factors of PC in Spain. MATERIALS AND METHODS: A multicentric, retrospective, observational epidemiological study was designed, and patients with a new diagnosis of PC in 2015 were included. Patients were anonymously identified from the Register of Specialized Care Activity of the Ministry of Health of Spain. All Spanish hospitals recruiting patients in 2015 were invited to participate in the present study. We have followed a descriptive narration of the observed data. Continuous and categorical data were reported by median (p25th-p75th range) and absolute and relative frequencies, respectively. The incidence map shows differences between Spanish regions. RESULTS: The incidence of PC in Spain in 2015 was 2.55/100,000 males per year. A total of 586 patients were identified, and 228 patients from 61 hospitals were included in the analysis. A total of 54/61 (88.5%) centers reported ≤ 5 new cases. The patients accessed the urologist for visually-assessed penile lesions (60.5%), mainly localized in the glans (63.6%). Local hygiene, smoking habits, sexual habits, HPV exposure, and history of penile lesions were reported in 48.2%, 59.6%, 25%, 13.2%, and 69.7%. HPV-positive lesions were 18.1% (28.6% HPV-16). The majority of PC was squamous carcinoma (95.2%). PC was ≥cT2 in 45.2% (103/228) cases. At final pathology, PC was ≥pT2 in 51% of patients and ≥pN1 in 17% of cases. The most common local treatment was partial penectomy (46.9% cases). A total of 47/55 (85.5%) inguinal lymphadenectomies were open. Patients with ≥pN1 disease were treated with chemotherapy in 12/39 (40.8%) of cases. CONCLUSIONS: PC incidence is relatively high in Spain compared to other European countries. The risk factors for PC are usually misreported. The diagnosis and management of PC are suboptimal, encouraging the identification of referral centers for PC management.

Conformations of diester triphenylphosphonium ylides with an ylidic ester or keto and ester ylidic groups.

The structures of three related keto diester and diester ylides, namely diethyl 3-oxo-2-(triphenylphosphoranylidene)glutarate, C(27)H(27)O(5)P, (I), diethyl 3-oxo-2-(triphenylphosphoranylidene)glutarate acetic acid monosolvate, C(27)H(27)O(5)P·C(2)H(4)O(2), (II), and diethyl 2-(triphenylphosphoranylidene)succinate, C(26)H(27)O(4)P, (III), are presented. The syn-keto anti-ester conformations in the crystalline keto diesters are governed by electronic delocalization between the P-C and ylidic bonds and an acyl group, and by intra- and intermolecular interactions. There are also intramolecular attractive and repulsive interactions of different types (C-H...O and C-H...π) controlling the molecular conformations. The mono-ylidic diester (III) has an anti-ester conformation, while those for (I) and (II) are related to pyrolytic formation of acetylene derivatives. The terminal nonylidic ester group in (I) was disordered over two sets of almost equally populated positions.

Assessing the Clinical Benefit of UBC Rapid in the Surveillance and Initial Diagnosis of Bladder Cancer.

INTRODUCTION: Several studies have shown that abnormal urine levels of cytokeratins 8 and 18 are associated with bladder cancer. However, the clinical benefit of the UBC (urinary bladder cancer) Rapid assay has remained unclear. PATIENTS AND METHODS: We performed the UBC Rapid assay and voided cytology in 336 patients-297 in surveillance for non-muscle-invasive bladder cancer and 39 with newly diagnosed bladder cancer. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated by contingency. We also controlled for the patients with positive UBC Rapid findings but negative cystoscopy findings to prove the former's ability to provide an anticipatory diagnosis. RESULTS: We diagnosed 27 recurrences (9.8%). Overall, the sensitivity of the UBC Rapid assay was better for the higher risk groups and after adding the cytology findings. The only independent predictor of a positive UBC Rapid assay was the tumor size. Of the 81 patients with positive UBC Rapid findings without positive cystoscopy findings, 8 (10%) had developed a recurrence within the first year. Avoiding cystoscopy for the patients with UBC Rapid negative results could avoid 184 cystoscopies (66%) but would result in missing 7 of 13 high-risk recurrences. CONCLUSIONS: The performance of the UBC Rapid assay improved with increasing tumor size. Limiting cystoscopies to patients with UBC Rapid positive results could result in a reduction in surveillance cystoscopies but could result in missing high-risk recurrences. Finally, the UBC Rapid assay was not useful for anticipatory diagnoses.

Genome Segregation by the Venus Flytrap Mechanism: Probing the Interaction Between the ParF ATPase and the ParG Centromere Binding Protein.

The molecular events that underpin genome segregation during bacterial cytokinesis have not been fully described. The tripartite segrosome complex that is encoded by the multiresistance plasmid TP228 in Escherichia coli is a tractable model to decipher the steps that mediate accurate genome partitioning in bacteria. In this case, a "Venus flytrap" mechanism mediates plasmid segregation. The ParG sequence-specific DNA binding protein coats the parH centromere. ParF, a ParA-type ATPase protein, assembles in a three-dimensional meshwork that penetrates the nucleoid volume where it recognizes and transports ParG-parH complexes and attached plasmids to the nucleoid poles. Plasmids are deposited at the nucleoid poles following the partial dissolution of the ParF network through a combination of localized ATP hydrolysis within the meshwork and ParG-mediated oligomer disassembly. The current study demonstrates that the conformation of the nucleotide binding pocket in ParF is tuned exquisitely: a single amino acid change that perturbs the molecular arrangement of the bound nucleotide moderates ATP hydrolysis. Moreover, this alteration also affects critical interactions of ParF with the partner protein ParG. As a result, plasmid segregation is inhibited. The data reinforce that the dynamics of nucleotide binding and hydrolysis by ParA-type proteins are key to accurate genome segregation in bacteria.

Structural insights into the calmodulin-Munc13 interaction obtained by cross-linking and mass spectrometry.

Munc13 proteins are essential regulators of synaptic vesicle priming and play a key role in adaptive synaptic plasticity phenomena. We recently identified and characterized the Ca(2+)-dependent interaction of Munc13 and calmodulin (CaM) as the molecular mechanism linking changes in residual Ca(2+) concentrations to presynaptic vesicle priming and short-term plasticity. Here, we used peptidic photoprobes covering the established CaM-binding motif of Munc13 for photoaffinity labeling (PAL) of CaM, followed by structural characterization of the covalent photoadducts. Our innovative analytical workflow based on isotopically labeled CaM and mass spectrometry revealed that, in the bound state, the hydrophobic anchor residue of the CaM-binding motif in Munc13s contacts two distinct methionine residues in the C-terminal domain of CaM. To address the orientation of the peptide during binding, we obtained additional distance constraints from the mass spectrometric analysis of chemically cross-linked CaM-Munc13 peptide adducts. The constraints from both complementary cross-linking approaches were integrated into low-resolution three-dimensional structure models of the CaM-Munc13 peptide complexes. Our experimental data are best compatible with the structure of the complex formed by CaM and a CaM-binding peptide derived from neuronal NO synthase and show that Munc13-1 and ubMunc13-2 bind to CaM in an antiparallel orientation through a 1-5-8 motif. The structural information about the CaM-Munc13 peptide complexes will facilitate the design of Munc13 variants with altered CaM affinity and thereby advance the detailed functional analysis of the role of Munc13 proteins in synaptic transmission and plasticity.

Atención médica de body packers en un territorio colombiano / Medical care for body packers in a Colombian territory

Introducción. El número de capturas a los body packers, que son aquellas personas que ingieren paquetes con estupefacientes para tráfico ilegal, ha aumentado paulatinamente. El objetivo de este estudio fue presentar los casos de body packers atendidos en dos instituciones de salud de Florencia, un territorio al sur de Colombia, entre 2003 y 2017. Métodos. Este es un estudio retrospectivo descriptivo. Se hizo un análisis univariado en RStudio y Microsoft Excel® de variables sociodemográficas y clínicas. Se emplearon medidas de tendencia central y dispersión para las variables continuas, frecuencias y proporciones para las variables categóricas. Resultados. Se incluyeron 72 pacientes. La mayoría de los casos fueron reportados entre 2007 y 2012 (77,5 %). La relación entre hombres y mujeres fue de 4,9:1. La edad media fue de 29,1 años. El principal motivo de admisión fue para chequeo médico tras captura por parte de los organismos de seguridad nacional (76,4 %). En 9 de cada 10 admitidos se realizaron estudios de imagen (94,4 %); la principal ayuda diagnóstica fue la radiografía de abdomen simple (84,7 %), con una sensibilidad del 91,6 %. Se realizó manejo expectante en tres de cada cuatro pacientes (74,6 %). El 6,9 % presentaron complicaciones, con una mortalidad (1,4 %). Conclusiones. La radiografía de abdomen simple es una ayuda diagnóstica adecuada para el tamizaje de los body packers. El manejo conservador es aceptable, teniendo en cuenta el porcentaje bajo de complicaciones.

Introduction. The number of arrests of body packers, who are those people who ingest packages with narcotics for illegal trafficking, has gradually increased. The objective of this study was to present the cases of body packers treated in two health institutions in Florencia, a territory in southern Colombia, between 2003 and 2017. Methods. This is a descriptive retrospective study. A univariate analysis was performed in RStudio and Microsoft Excel® of sociodemographic and clinical variables. Measures of central tendency and dispersion were used for continuous variables, frequencies and proportions for categorical variables. Results. 72 patients were included. Most cases were reported between 2007 and 2012 (77.5%). The ratio between men and women was 4.9:1. The mean age was 29.1 years. The main reason for admission was for medical check-up after capture by national security agencies (76.4%). In nine out of ten admitted patients, imaging studies were performed (94.4%); the main diagnostic imaging was simple abdominal X-ray (84.7%), with a sensitivity of 91.6%. Expectant management was performed in three out of four patients (74.6%). 6.9% presented complications, with one mortality (1.4%). Conclusions. Simple abdominal x-ray is an adequate diagnostic tool for screening body packers. Conservative management is acceptable, taking into account the low percentage of complications.

Favoured conformations of methyl isopropyl, ethyl isopropyl, methyl tert-butyl, and ethyl tert-butyl 2-(triphenylphosphoranylidene)malonate.

The conformations of organic compounds determined in the solid state are important because they can be compared with those in solution and/or from theoretical calculations. In this work, the crystal and molecular structures of four closely related diesters, namely methyl isopropyl 2-(triphenylphosphoranylidene)malonate, C(25)H(25)O(4)P, ethyl isopropyl 2-(triphenylphosphoranylidene)malonate, C(26)H(27)O(4)P, methyl tert-butyl 2-(triphenylphosphoranylidene)malonate, C(26)H(27)O(4)P, and ethyl tert-butyl 2-(triphenylphosphoranylidene)malonate, C(27)H(29)O(4)P, have been analysed as a preliminary step for such comparative studies. As a result of extensive electronic delocalization, as well as intra- and intermolecular interactions, a remarkably similar pattern of preferred conformations in the crystal structures results, viz. a syn-anti conformation of the acyl groups with respect to the P atom, with the bulkier alkoxy groups oriented towards the P atom. The crystal structures are controlled by nonconventional hydrogen-bonding and intramolecular interactions between cationoid P and acyl and alkoxy O atoms in syn positions.

Two new chiral EDTA-based metal chelates for weak alignment of proteins in solution.

[structure: see text] A short synthesis of EDTA-based metal chelates that can be attached to the cysteine residue of a protein via a disulfide bond is described. The complexes were used after coordination of lanthanides to align trigger factor and apo-calmodulin in solution to yield residual dipolar couplings and pseudocontact shifts. Alignment tensors for the new tags are linearly independent compared to those of previously published tags.

Ethylene glycol-assisted coating of titania on nanoparticles.

Coating titania shells onto sub-micron sized particles has been widely studied recently, with success mainly limited to objects with sizes above 50 nm. Direct coating on particles below this size has been difficult to attain especially with good control over properties such as thickness and crystallinity. Here we demonstrate that titanium-glycolate formed by reacting titanium alkoxide and ethylene glycol is an excellent precursor for coating titania on aqueous nanoparticles. The new coating method is particularly useful for its ability to coat materials lacking strong polymers or ligands which are frequently needed to facilitate typical titania coatings. We demonstrate the effectiveness of the process of coating titania on metal nanoparticles ranging from citrate-stabilized gold and silver spheres to gold nanorods and silver nanoplates, and larger particles such as SiO2 microspheres and polymer spheres. Further the thickness of these coatings can be tuned from a few nanometers to ∼40 nm through sequential coatings. These coatings can subsequently be crystallized into TiO2 through refluxing in water or by calcination to obtain crystalline shells. This procedure can be very useful for the production of TiO2 coatings with tunable thickness and crystallinity as well as for further study on the effect of TiO2 coatings on nanoparticles.

Human Papillomavirus Type 18 cis-Elements Crucial for Segregation and Latency.

Stable maintenance replication is characteristic of the latency phase of HPV infection, during which the viral genomes are actively maintained as extrachromosomal genetic elements in infected proliferating basal keratinocytes. Active replication in the S-phase and segregation of the genome into daughter cells in mitosis are required for stable maintenance replication. Most of our knowledge about papillomavirus genome segregation has come from studies of bovine papillomavirus type 1 (BPV-1), which have demonstrated that the E2 protein cooperates with cellular trans-factors and that E2 binding sites act as cis-regulatory elements in the viral genome that are essential for the segregation process. However, the genomic organization of the regulatory region in HPVs, and the properties of the viral proteins are different from those of their BPV-1 counterparts. We have designed a segregation assay for HPV-18 and used it to demonstrate that the E2 protein performs segregation in combination with at least two E2 binding sites. The cooperative binding of the E2 protein to two E2 binding sites is a major determinant of HPV-18 genome segregation, as demonstrated by the change in spacing between adjacent binding sites #1 and #2 in the HPV-18 Upstream Regulatory Region (URR). Duplication or triplication of the natural 4 bp 5'-CGGG-3' spacer between the E2 binding sites increased the cooperative binding of the E2 molecules as well as E2-dependent segregation. Removal of any spacing between these sites eliminated cooperative binding of the E2 protein and disabled segregation of the URR and HPV-18 genome. Transfer of these configurations of the E2 binding sites into viral genomes confirmed the role of the E2 protein and binding sites #1 and #2 in the segregation process. Additional analysis demonstrated that these sites also play an important role in the transcriptional regulation of viral gene expression from different HPV-18 promoters.

Structures of archaeal DNA segregation machinery reveal bacterial and eukaryotic linkages.

Although recent studies have provided a wealth of information about archaeal biology, nothing is known about the molecular basis of DNA segregation in these organisms. Here, we unveil the machinery and assembly mechanism of the archaeal Sulfolobus pNOB8 partition system. This system uses three proteins: ParA; an atypical ParB adaptor; and a centromere-binding component, AspA. AspA utilizes a spreading mechanism to create a DNA superhelix onto which ParB assembles. This supercomplex links to the ParA motor, which contains a bacteria-like Walker motif. The C domain of ParB harbors structural similarity to CenpA, which dictates eukaryotic segregation. Thus, this archaeal system combines bacteria-like and eukarya-like components, which suggests the possible conservation of DNA segregation principles across the three domains of life.

1H, 13C and 15N resonance assignments of the Calmodulin-Munc13-1 peptide complex.

Ca(2+)-Calmodulin binding to the variable N-terminal region of the diacylglycerol/phorbol ester-binding UNC13/Munc13 family of proteins modulates the short-term synaptic plasticity characteristics in neurons. Here, we report the sequential backbone and side chain resonance assignment of the Ca(2+)-Calmodulin/Munc13-1(458-492) peptide complex at pH 6.8 and 35 degrees C (BMRB No. 15470).

Cyano-stabilized triphenylphosphonium ylids.

Crystalline cyano-stabilized triphenylphosphonium ylids with keto or ester groups give rise to an extended electronic delocalization. In methyl 2-cyano-2-(trimethylphosphonio)ethenoate, Ph3P=C(CN)CO2CH3 or C22H18NO2P, (I), and 1-cyano-1-(trimethylphosphonio)prop-1-en-2-olate, Ph3P=C(CN)CO-CH3 or C22H18NOP, (II), the carbonyl groups are oriented toward the cationoid P atom. Bond lengths and angles, torsion angles and P...O contact distances are consistent with a dominant coplanar conformation where the molecular structures are the result of a balance between intra- and intermolecular interactions. The main interactions presented by cyano-ester (I) and cyano-keto (II) are intramolecular interactions between the carbonyl O and the P atoms. In addition, both compounds show other less important intramolecular interactions between the carbonyl O and phenyl H atoms, which could contribute to form a preferred conformation in the crystal structure.