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•A low frequency of Vγ9Vδ2 T cells in AML is an independent predictor of poor clinical outcome.•These data provide a strong rationale for the development of consolidation protocols aimed at enhancing Vγ9Vδ2 T-cell responses.

We study the origin of bimodal emission in AlGaN/AlN QD superlattices displaying a high internal quantum efficiency (around 50%) in the 230–300 nm spectral range. The secondary emission at longer wavelengths is linked to the presence of cone-like domains with deformed QD layers, which originate at the first AlN buffer/superlattice interface and propagate vertically. The cones originate at a 30°-faceted shallow pit in the AlN, which appears to be associated with a threading dislocation that produces strong shear strain. The cone-like structures present Ga enrichment at the boundaring facets and larger QDs within the conic domain. The bimodality of the luminescence is attributed to the differing dot size and composition within the cones and at the faceted boundaries, which is confirmed by the correlation of microscopy results and Schro¨dinger–Poisson calculations.

La maladie de Cacchi Ricci (MCR) est une pathologie rare, caractérisée par la dilatation précalicielle des tubes rénaux, dont le diagnostic est difficile et la physiopathologie incomprise. Plusieurs anomalies tubulaires ont été décrites suggérant une altération de la fonction médullaire. Afin de mieux caractériser ces patients, il est nécessaire de mettre au point des outils pour évaluer la structure rénale et la fonction médullaire. Cela est désormais permis par l’imagerie par résonance magnétique fonctionnelle (IRMf) qui peut évaluer la performance rénale via notamment la séquence BOLD (blood oxygen level dependent) qui mesure l’oxygénation tissulaire.

Les patients présentant une lésion PIRADS 5 ont un surrisque de cancer de la prostate (CaP) cliniquement significatif. Dans ce contexte, la découverte d’un CaP à faible risque peut remettre en cause la décision de surveillance active (SA), notamment en raison du risque d’upstagingsur la pièce de prostatectomie. Cette étude rapporte la survie de patients présentant un CaP avec une lésion PIRADS 5 traités par SA.

Primary Coenzyme Q10 deficiency is a rare mitochondriopathy with a wide spectrum of organ involvement, including steroid-resistant nephrotic syndrome mainly associated with disease-causing variants in the genes COQ2, COQ6or COQ8B. We performed a systematic literature review, PodoNet, mitoNET, and CCGKDD registries queries and an online survey, collecting comprehensive clinical and genetic data of 251 patients spanning 173 published (47 updated) and 78 new cases. Kidney disease was first diagnosed at median age 1.0, 1.2 and 9.8 years in individuals with disease-causing variants in COQ2, COQ6 and COQ8B, respectively. Isolated kidney involvement at diagnosis occurred in 34% of COQ2, 10.8% of COQ6and 70.7% of COQ8Bvariant individuals. Classic infantile multiorgan involvement comprised 22% of the COQ2variant cohort while 47% of them developed neurological symptoms at median age 2.7 years. The association of steroid-resistant nephrotic syndrome and sensorineural hearing loss was confirmed as the distinctive phenotype of COQ6variants, with hearing impairment manifesting at average age three years. None of the patients with COQ8Bvariants, but 50% of patients with COQ2and COQ6variants progressed to kidney failure by age five. At adult age, kidney survival was equally poor (20-25%) across all disorders. A number of sequence variants, including putative local founder mutations, had divergent clinical presentations, in terms of onset age, kidney and non-kidney manifestations and kidney survival. Milder kidney phenotype was present in those with biallelic truncating variants within the COQ8Bvariant cohort. Thus, significant intra- and inter-familial phenotype variability was observed, suggesting both genetic and non-genetic modifiers of disease severity.

The objective of this study was to analyze the dose-dependent safety profiles of stereotactic body radiation therapy (SBRT) in patients with inoperable small renal cell carcinoma (RCC).

Le système nerveux central (SNC) (méningite carcinomateuse ou métastases solides cérébrales) est un site de récidive très fréquent des cancers bronchiques non à petites cellules (CBNPC) porteurs d’anomalies activatrices.

Prostate multi-parametric magnetic resonance imaging (mpMRI) has shown excellent sensitivity for Gleason ≥7 cancers, especially when their volume is ≥0.5 mL. As a result, performing an mpMRI before prostate biopsy could improve the detection of clinically significant prostate cancer (csPCa) by adding targeted biopsies to systematic biopsies. Currently, there is a consensus that targeted biopsies improve the detection of csPCa in the repeat biopsy setting and at confirmatory biopsy in patients considering active surveillance. Several prospective multicentric controlled trials recently showed that targeted biopsy also improved csPCa detection in biopsy-naïve patients. The role of mpMRI and targeted biopsy during the follow-up of active surveillance remains unclear. Whether systematic biopsy could be omitted in case of negative mpMRI is also a matter of controversy. mpMRI did show excellent negative predictive values (NPV) in the literature, however, since NPV depends on the prevalence of the disease, negative mpMRI findings should be interpreted in the light of a prioririsk for csPCa of the patient. Nomograms combining mpMRI findings and classical risk predictors (age, prostate-specific antigen density, digital rectal examination, etc.) will probably be developed in the future to decide whether a prostate biopsy should be obtained. mpMRI has a good specificity for detecting T3 stage cancers, but its sensitivity is low. It should therefore not be used routinely for staging purposes in low-risk patients. Nomograms combining mpMRI findings and other clinical and biochemical data will also probably be used in the future to better assess the risk of T3 stage disease.

There has been extensive activity exploring the doping of semiconducting two-dimensional (2D) transition metal dichalcogenides in order to tune their electronic and magnetic properties. The outcome of doping depends on various factors, including the intrinsic properties of the host material, the nature of the dopants used, their spatial distribution, as well as their interactions with other types of defects. A thorough atomic-level analysis is essential to fully understand these mechanisms. In this work, the vanadium-doped WSe2monolayer grown by molecular beam epitaxy is investigated using four-dimensional scanning transmission electron microscopy (4D-STEM). Through center-of-mass-based reconstruction, atomic-scale maps are produced, allowing the visualization of both the electric field and the electrostatic potential around individual V atoms. To provide quantitative insights, these results are successfully compared to multislice image simulations based on ab initio calculations, accounting for lens aberrations. Finally, a negative charge around the V dopants is detected as a drop in the electrostatic potential, unambiguously demonstrating that 4D-STEM can be used to detect and to accurately analyze single-dopant charge states in semiconducting 2D materials.

The determination of size variants is a major critical quality attribute of a therapeutic monoclonal antibody (mAb that may affect the drug product safety, potency, and efficacy. Size variant characterization often relies on size-exclusion chromatography (SEC), which could be hampered by difficult identification of peaks. On the other hand, mass spectrometry (MS)-based techniques performed in nondenaturing conditions have proven to be valuable for mAb-related compound characterization. On the basis of the observation that limited SEC performance was observed in nondenaturing MS compatible ammonium acetate buffer compared with classical phosphate salts, a multidimensional analytical approach was proposed. It combines comprehensive online two-dimensional chromatography (SEC×SEC), with ion mobility and mass spectrometry (IM-MS) in nondenaturing conditions for the characterization of a variety of mAbs. We first exemplify the versatility of our approach for simultaneous detection, identification, and quantitation of adalimumab size variants. Benefits of the SEC×SEC-native IM×MS were further highlighted on forced degraded pembrolizumab and bevacizumab samples, for which the 4D setup was mandatory to obtain an extensive and unambiguous identification, and accurate quantitation of unexpected high/low molecular weight species (HMWS and LMWS). In this specific context, monomeric conformers were detected by IM-MS as HMWS or LMWS. Altogether, our results emphasize the power of comprehensive 2D LC×LC setups hyphenated to IM×MS in nondenaturing conditions with unprecedented performance including: (i) maintaining optimal SEC performance (under classical nonvolatile salt conditions), (ii) performing online native MS identification, and (iii) providing IM-MS conformational characterization of all separated size variants.

Objectif Comparer les résultats fonctionnels et carcinologiques à 1 an d’un traitement focal par HIFU et par prostatectomie totale (PT) pour cancer localisé de la prostate (CaP) localisé.

By mole, cholesterol is the most abundant component of animal cell plasma membranes. Many membrane proteins have been shown to be functionally dependent on cholesterol, several of which have also been shown to bind cholesterol at well-defined locations on their membrane-facing surface. In this work, a combination of coarse-grained “Martini” and all-atom simulations are used to identify two, to our knowledge, new cholesterol-binding sites on the A2Aadenosine receptor, a G-protein-coupled receptor that is a target for the treatment of Parkinson’s disease. One of the sites is also observed to bind cholesterol in several recent, high-resolution crystal structures of the protein, and in the simulations, interacts with cholesterol only when bound to the inverse agonist ZM241385. Cataloguing cholesterol-binding sites is a vital step in the effort to understand cholesterol-dependent function of membrane proteins. Given that cholesterol content in plasma membranes varies with cell type and on administration of widely prescribed pharmaceuticals, such as statins, understanding cholesterol-dependent function is an important step toward exploiting membrane compositional variation for therapeutic purposes.

We report bandgap engineering of Ge rich SiGe rib waveguides between 1550 nm and 1580 nm through an annealing process. The insertion loss of the material (transmission spectrum) is analysed between 1520 nm and 1600 nm. The experimental data are elaborated by implementing the Tauc Method analysis, and the material bandgap estimation is calculated. A maximum blue shift of 38 nm, with an overall reduction of Si content, suggests that the diffusion of Si in the Ge seed layer during anneal improves the homogeneity of the growth layer. The proposed technique provides a path for tailoring the operational wavelength of devices such as electro-absorption modulators, realized on an SOI platform.

This protocol details the step-by-step procedure for in-depth immune phenotyping of peripheral blood natural killer (NK) cells from clinical samples by mass cytometry. The protocol consists of three main steps: PBMC incubation with a mix of metal-conjugated antibodies for extracellular phenotyping followed by fixation, permeabilization and incubation with a mix of metal-conjugated antibodies for staining of intracellular proteins, and sample acquisition on a mass cytometer. High-dimensional analysis enables the visualization of NK cell subsets and their phenotypical characteristics.

La récidive locale après chirurgie puis radiothérapie (adjuvante ou de rattrapage) est une situation problématique et identifiée de plus en plus souvent grâce au PET scanner (choline ou PSMA).

Les mécanismes de la cancérogenèse sont de mieux en mieux décryptés depuis une vingtaine d’années. Les principales anomalies moléculaires motrices dans le domaine de l’oncologie thoracique sont actuellement les mutations de l’EGFR, de KRAS, ainsi que la translocation EML4-ALK. Elles sont le plus souvent rapportées dans les adénocarcinomes. Néanmoins, de nouvelles cibles moléculaires ont été mises en évidence récemment telles que les mutations de BRAF, de HER2 ou de PI3K, de nouvelles translocations telles que ROS1 ou KIF5B-RETet enfin de nouvelles anomalies moléculaires dans des tumeurs autres que les adénocarcinomes (épidermoïdes et cancers à petites cellules). De nombreuses stratégies thérapeutiques sont étudiées pour bloquer ces voies de signalisation. Les deux principales sont les anticorps monoclonaux ciblant le ligand ou son récepteur et les inhibiteurs de l’activité tyrosine kinase (TKI) de ces protéines. Certaines de ces molécules sont commercialisées, d’autres sont en cours d’étude clinique. Nous proposons, dans cette revue, de rapporter les nouvelles cibles et les traitements prometteurs qui s’y rapportent.

High-intensity focused ultrasound (HIFU) has been widely used for whole gland ablation with large series. HIFU induces immediate and irreversible coagulative necrosis with sharply delineated boundaries making HIFU an attractive treatment option for focal therapy of localized prostate. The treatment can be accurately targeted to a portion of the prostate gland. Unlike radiation, there is no lifetime dose limit, allowing HIFU to be repeated if necessary. Additional radical therapy can be performed involving radical surgery, external beam radiation therapy and cryotherapy. Moreover, HIFU is a minimally invasive therapy that can be performed under spinal anesthesia on an outpatient basis.

Prostate cancer is the most common malignancy among men yet no current imaging technique is capable of detecting the tumours with precision. To evaluate each technique, the histology data must be precisely mapped to the imaged data. As it cannot be assumed that the histology slices are cut along the same plane as the imaged data is acquired, the registration is a 3D problem. This requires the prior accurate alignment of the histology slices. We propose a protocol to create in a rapid and standardised manner internal fiducial markers in fresh prostate specimens and an algorithm by which these markers can then be automatically detected and classified enabling the automatic rigid alignment of each slice. The protocol and algorithm were tested on 10 prostate specimens, with 19.2 histology slices on average per specimen. On average 90.9% of the fiducial markers created were visible in the slices, of which 96.1% were automatically correctly detected and classified. The average accuracy of the alignment was 0.19 ± 0.15 mm at the fiducial markers. The algorithm took 5.46 min on average per specimen. The proposed protocol and algorithm were also tested using simulated images and a beef liver sample. The simulated images showed that the algorithm has no associated residual error and justified the choice of a rigid registration. In the beef liver images, the average accuracy of the alignment was 0.11 ± 0.09 mm at the fiducial markers and 0.63 ± 0.47 mm at a validation marker approximately 20 mm from the fiducial markers.

Different technologies for the fabrication of Germanium photodetectors were developed. Germanium was grown by RPCVD in a silicon cavity in order to provide a direct coupling with a rib silicon waveguide. With direct deposition of Ti/TiN/AlCu on Ge, Metal-Schotkky-Metal (MSM) diodes were formed. PIN photodiode were fabricated either with in-situ doping during RP- CVD epitaxy of Ge, either by ion implantation. For vertical PIN photodiode, the germanium was successfully etched either in mesa either anisotropically with Cl2 gazes. Small footprint Ge photodiodes can lead to high speed operation on CMOS

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology.

HU, a major component of the bacterial nucleoid, shares properties with histones, high mobility group proteins (HMGs), and other eukaryotic proteins. HU, which participates in many major pathways of the bacterial cell, binds without sequence specificity to duplex DNA but recognizes with high affinity DNA repair intermediates. Here we demonstrate that HU binds to double-stranded DNA, double-stranded RNA, and linear DNA-RNA duplexes with a similar low affinity. In contrast to this nonspecific binding to total cellular RNA and to supercoiled DNA, HU specifically recognizes defined structures common to both DNA and RNA. In particular HU binds specifically to nicked or gapped DNA-RNA hybrids and to composite RNA molecules such as DsrA, a small non-coding RNA. HU, which modulates DNA architecture, may play additional key functions in the bacterial machinery via its RNA binding capacity. The simple, straightforward structure of its binding domain with two highly flexible β-ribbon arms and an α-helical platform is an alternative model for the elaborate binding domains of the eukaryotic proteins that display dual DNA- and RNA-specific binding capacities.

Purpose: Carotid artery stenting (CAS) appears as a promising alternative treatment to carotid endarterectomy for radiation therapy (RT)-induced carotid stenosis. However, this is based on a poor level of evidence studies (small sample size, primarily single institution reports, few long-term data). The purpose of this study was to report the long-term outcomes of a multicentric series of CAS for RT-induced stenosis.Methods: All CAS for RT-induced stenosis performed in 11 French academic institutions from 2005 to 2017 were collected in this retrospective study. Patient demographics, clinical risk factors, elapsed time from RT, clinical presentation and imaging parameters of carotid stenosis were preoperatively gathered. Long-term outcomes were determined by clinical follow-up and duplex ultrasound. The primary endpoint was the occurrence of cerebrovascular events during follow-up. Secondary endpoints included perioperative morbidity and mortality rate, long-term mortality rate, primary patency, and target lesion revascularization.Results: One hundred and twenty-one CAS procedures were performed in 112 patients. The mean interval between irradiation and CAS was 15 ± 12 years. In 31.4% of cases, the lesion was symptomatic. Mean follow-up was 42.5 ± 32.6 months (range 1–141 months). The mortality rate at 5 years was 23%. The neurologic event-free survival and the in-stent restenosis rates at 5 years were 87.8% and 38.9%, respectively. Diabetes mellitus (p=0.02) and single postoperative antiplatelet therapy (p=0.001) were found to be significant predictors of in-stent restenosis. Freedom from target lesion revascularization was 91.9% at 5 years.Conclusion: This study showed that CAS is an effective option for RT-induced stenosis in patients not favorable to carotid endarterectomy. The CAS was associated with a low rate of neurological events and reinterventions at long-term follow-up.

A key issue in the development of high-performance semiconductor devices is the ability to properly measure active dopants at the nanometer scale. In a p–n junction, the abruptness of the dopant profile around the metallurgical junction directly influences the electric field. Here, a contacted nominally symmetric and highly doped (NA= ND= 9 × 1018cm–3) silicon p–n specimen is studied through in situ biased four-dimensional scanning transmission electron microscopy (4D-STEM). Measurements of electric field, built-in voltage, depletion region width, and charge density are combined with analytical equations and finite-element simulations in order to evaluate the quality of the junction interface. It is shown that all the junction parameters measured are compatible with a linearly graded junction. This hypothesis is also consistent with the evolution of the electric field with bias as well as off-axis electron holography data. These results demonstrate that in situ biased 4D-STEM can allow a better understanding of the electrostatics of semiconductor p–n junctions with nm-scale resolution.

Présentation des résultats fonctionnels et oncologiques à long termes des HIFU de rattrapage des récidives locales après radiothérapie.

We have shown recently that the relative abundance of the three dimeric forms (α2, αβ and β2) of the HU protein from Escherichia coli varies during growth and in response to environmental changes. Using gel retardation assays we have compared the DNA binding properties of the three dimers with different DNA substrates. The determination of their DNA binding parameters shows that the relative affinities of HUαβ and HUα2 are comparable. Both recognize, with a high degree of affinity under stringent conditions, cruciform structures or DNA molecules with a nick or a gap, whereas they bind to linear DNA only at low salt. DNA containing a gap of two nucleotides is in fact the substrate recognized with the highest degree of affinity by these two forms under all conditions. Conversely, HUβ2 binds very poorly to duplex DNA and shows a much lower affinity for nicked or gapped DNAs. However, HUβ2 binds to cruciform DNA structures almost as well as HUαβ and HUα2. This almost exclusive binding of HUβ2 to a unique substrate is surprising in regards of the quasi identity, in the three forms, of the flexible arms considered as the DNA-binding domains of the three forms of HU. Cruciform DNA may stabilize HUβ2 structure which could be structurally defective.

The histone‐like protein HU isolated from E. coliis well conserved in prokaryotes. We show here that antiserum prepared against bacterial HU cross‐reacts with a DNA‐binding protein co‐sedimenting with the nucleoid of spinach chloroplasts. Antibodies prepared against cyanobacterial HU are more reactive than those raised against E. coliHU. The chloroplast protein resembles HU in that both appear to be composed of two related subunits.

To understand the mechanism by which the serum response factor (SRF) is involved in the process of skeletal muscle differentiation, we have assessed the effect of inhibiting SRF activity or synthesis on the expression of the muscle-determining factor MyoD. Inhibition of SRF activity in mouse myogenic C2C12 cells through microinjection of either the SRE oligonucleotide (which acts by displacing SRF proteins from the endogenous SRE sequences), purified SRF-DB (a 30-kDa portion of SRF containing the DNA-binding domain of SRF, which acts as a dominant negative mutant in vivo), or purified anti-SRF antibodies rapidly prevents the expression of MyoD. Moreover, the rapid shutdown of MyoD expression after in vivo inhibition of SRF activity is observed not only in proliferating myoblasts but also in myoblasts cultured under differentiating conditions. Additionally, by using a cellular system expressing a glucocorticoid-inducible antisense-SRF (from aa 74 to 244) we have shown that blocking SRF expression by dexamethasone induction of antisense SRF results in the lack of MyoD expression as probed by both immunofluorescence and Northern blot analysis. Taken together these data demonstrate that SRF expression and activity are required for the expression of the muscle-determining factor MyoD.

Resumé Les propriétés physico-chimiques de solutions aqueuses de différents alkyl-p-benzènesulfonates de pureté contrôlée ont été déterminées par diverses méthodes: solubilité, viscosité, autodiffusions. Les micelles formées par len-octyl-p-benzènesulfonate de sodium (C8f SO3 Na) et len-dodécyl-p-benzènesul-fornate de sodium (C12f Na) sont globulaires dans tout le domaine de concetration exploité; les micelles (C8f SO3 Na + C12f SO3 Na) sont de taille proche de celles de C8f SO3 Na.

Let L_χ be the line bundle over a symmetric space G/H defined by a character χ of H. We transfer to the tangent space to G/H, by means of the exponential map, invariant differential operators and distributions on L_χ. Relying on a detailed study of this correspondence, we obtain general expressions for convolution of H-invariant distributions and for G-invariant differential operators and their composition product. In particular, for certain characters χ, these results imply commutativity of the convolutions and give a geometric proof of Duflo's theorem on the commutativity of the algebra of invariant differential operators on L_χ.Copyright 1994, 1999 Academic Press, Inc.

The histone-like dimeric HU protein of Escherichia coli is encoded by two closely related genes, hupA and hupB. We show here that expression from the single hupA promoter and from the three hupB promoters varies during growth phase. The weak hupB-P4 promoter is active immediately after dilution. Transcription of the hupA gene is activated early in logarithmic phase. A little later, at mid to late exponential phase, RNA originating at the hupB-P2 promoter is detected. The hupB-P3 promoter is activated last when the cells enter stationary phase. Although the hup mRNAs are unstable, the HU protein is very stable so that the variations in the mRNAs synthesis are reflected in the level of the two HU subunits and in the composition of HU dimers. Cells growing exponentially contain a mixture of homodimeric α2 and heterodimeric αβ but no β2 is detected. In stationary cells, the predominant form is the heterodimer αβ. The presence of the heterodimeric form is required for optimal survival of E. coli after prolonged starvation. The three forms of HU are not equivalent, since β2 is incapable of promoting formation of DNA supercoiling like αβ and α2 do. The putative roles of each form of HU are discussed.

We have recently identified a 6,449 bp cDNA, termed colonic, hepatic tumor over-expressed gene (ch-TOG), that is highly expressed in human tumors and brain. Its single open reading frame encodes a putative 218,000 Da polypeptide, TOGp. Antibodies generated against a bacterially expressed TOGp fragment specifically recognize a 218, 000 Da polypeptide in two human cell lines and in brain. Immunofluorescence microscopy using affinity-purified TOGp antibodies revealed that the distribution of TOGp was dependent upon the cell cycle. During interphase, TOGp was found concentrated in the perinuclear cytoplasm, where it co-localized with ER markers. In contrast anti-TOGp antibodies stained centrosomes and spindles in mitotic cells. TOGp co-sedimented with taxol-stabilized microtubules in vitro. Moreover, a TOGp enriched fraction promotes microtubule assembly both in solution and from nucleation centers. Finally, sequence comparison and immunologic cross-reaction suggest that TOGp is homologous to XMAP215, a previously described microtubule associated protein (MAP) from Xenopus eggs. These results suggest that TOGp is a MAP and that TOGp/XMAP215 may be necessary for microtubules rearrangements and spindle assembly in rapidly dividing cells.

We have previously studied the binding characteristics of the HU protein of Escherichia coli to different linear DNAs. In this work, using gel-retardation and footprint analysis, we studied the specific binding of HU protein to a synthetic cruciform DNA. We have quantified our results in order to precisely define the binding and cooperativity constants of HU protein towards cruciform DNA and compare them to those obtained linear DNA. We used stringent high-salt conditions versus non-stringent low-salt condition in order to differentiate the non-specific-protein HU-DNA complexes from the specific, high-salt-resistant complexes. We observed that HU-protein dimers bind specifically to the cruciform DNA with a binding constant K = 2·0 × 10⁸ M-¹ and a value for the cooperativity constant ω = 1 corresponding to a non-cooperative phenomenon. For the first time we observe a footprint pattern of HU protein bound to DNA using the hydroxyl-radical-footprinting technique on HU-protein-cruciform-DNA complexes. The residues protected by HU protein are localized at and near the junction point but interesting they are mainly present in two of the four oligonucleotides which constitute the cruciform DNA. These two oligonucleotides are unpaired and opposite each other. These results support a model where two HU-protein dimers specifically bind to two equivalent angles present opposite each other in the four-way-junction-DNA structure with almost no dimer-dimer interactions. Copyright 1994, 1999 Academic Press