Comparative study of calcification in human choroid plexus, pineal gland, and habenula.

Choroid plexus, pineal gland, and habenula tend to accumulate physiologic calcifications (concrements) over a lifetime. However, until now the composition and causes of the intracranial calcifications remain unclear. The detailed analysis of concrements has been done by us using X-ray diffraction analysis (XRD), X-ray diffraction topography (XRDT), micro-CT, X-ray phase-contrast tomography (XPCT), as well as histology and immunohistochemistry (IHC). By combining physical (XRD) and biochemical (IHC) methods, we identified inorganic (hydroxyapatite) and organic (vimentin) components of the concrements. Via XPCT, XRDT, histological, and IHC methods, we assessed the structure of concrements within their appropriate tissue environment in both two and three dimensions. The study found that hydroxyapatite was a major component of all calcified depositions. It should be noted, however, that the concrements displayed distinctive characteristics corresponding to each specific structure of the brain. As a result, our study provides a basis for assessing the pathological and physiological changes that occur in brain structure containing calcifications.

Volatile fatty acid platform - a cornerstone for the circular bioeconomy.

Annually, the EU produces more than 100 million tonnes of urban biowaste, which is largely under-valorized and in some cases even still landfilled without any energy or material recovery. If Europe wants to be ready for the future, it will need to make better use of this large biomass potential within a circular economy approach. The research project funded by the European Commission under the Horizon 2020 programme entitled 'VOLATILE-Biowaste derived volatile fatty acid platform for biopolymers, bioactive compounds and chemical building blocks' aimed to produce volatile fatty acids (VFAs) from biowaste for reprocessing into products, materials or substances to close the material loop. During the project, the partners were able to obtain average volatile fatty acid yields of 627 g COD/kg organic matter (OM) for food waste, 448 g COD/kg OM for separately collected vegetable, garden and fruit waste (VGF) and 384 g COD/kg OM for the organic fraction of municipal solid waste (OF-MSW) at concentrations ranging from 12 to 48 g/L, 6 to 40 g/L and 13 to 26 g/L, respectively. A membrane filtration cascade consisting of micro-, ultra- and nano-filtration followed by reverse osmosis was identified as a feasible way to purify and concentrate the VFA effluent, making them a suitable carbon source for further fermentation processes. Besides technical optimization, socio-economic and legal aspects associated with this platform technology were also studied and show that although this technology is still in development, it is providing an answer to changing societal and market expectations both regarding organic waste treatment and bio-based production strategies. Based on the current technological, economic and market evolutions, it is expected that the VFAP will play an important role in organic waste treatment in the coming years.

Clinical Accuracy of 3D-Planned Maxillary Positioning Using CAD/CAM-Generated Splints in Combination With Temporary Mandibular Fixation in Bimaxillary Orthognathic Surgery.

STUDY DESIGN: The aim of this study was to evaluate the accuracy of 3-dimensional (3D)-planned maxillary positioning by using computer-assisted design (CAD)/computer-assisted manufacturing (CAM) splints combined with temporary mandibular fixation in bimaxillary orthognathic surgery. In orthognathic surgery, customized splints work sufficiently well to transfer preoperative planning into the operation site for transverse und sagittal positioning of the maxilla. The vertical positioning is more difficult due to the non-fixed mandibular reference. Therefore, the combined use of CAD/CAM splints and temporary mandibular fixation to the zygomatic region was applied for transferring the 3D-planned maxillary position into the operation site from 2012 until 2015 in our hospital. OBJECTIVE: In addition to the general accuracy, the precision should therefore be checked especially in the vertical plane compared to axial and sagittal plane. METHODS: In this retrospective study, we calculated the deviation of 5 occlusal landmarks of the maxilla in 35 consecutive patients by fusing preoperative 3D planning images and postoperative computed tomography scans after bimaxillary surgery. RESULTS: The overall median deviation of maxillary positioning between plan and surgical result was 0.99 mm. The accuracy of left-right positioning was median 0.96 mm. Anterior-posterior positioning of the maxilla showed a median accuracy of 0.94 mm. Just slightly higher values were determined for the upward-downward positioning (median 1.06 mm). CONCLUSIONS: This demonstrates the predictability of maxillary positioning by using CAD/CAM splints in combination with temporary mandibular fixation in all 3 axes.

Custom wave-shaped CAD/CAM orbital wall implants for the management of post-enucleation socket syndrome.

The satisfactory management of post-enucleation socket syndrome is a major challenge. In addition to enophthalmos and hypophthalmos, the appearance of the supratarsal fold is frequently unsatisfactory. Using a combination of orbital volume reduction by means of custom wave-shaped CAD/CAM implants (1), the implantation of a dermis-fat graft (2), and the fitting of an acrylic eye prothesis (3), an algorithm has been developed that has led to considerable long-term improvements. 10 patients have already been treated by this method. The most important step is the reduction of orbital volume by means of custom wave-shaped CAD/CAM implants. These move the intraorbital soft tissue in an anterior and cranial direction. This considerably reduces the required volume of additional dermis-fat grafts, which are always subject to resorption. The use of an acrylic eye prothesis facilitates the aesthetic and functional correction of this condition and exerts less pressure on the lower eyelid due to its low weight. The method presented here leads to stable and aesthetically pleasing results with a minimum risk of complications. One problem is the exact predictability of the necessary orbital volume reduction by the custom wave-shaped CAD/CAM implants. Further studies and a larger number of cases are required to address this problem.

Validity of sentinel node biopsy in early oral and oropharyngeal carcinoma.

PURPOSE: This study investigates the possibility and sensibility of using sentinel node biopsy (SNB) during surgery for oropharyngeal carcinomas with clinically and radiographically unremarkable cervical lymph nodes. MATERIALS AND METHODS: A total of 36 patients who were treated for early oral and oropharyngeal carcinoma and unremarkable cervical lymph nodes were included in this study. After lymphoscintigraphy for detecting sentinel lymph nodes (SLN), the SLN were excised first. Thereafter elective neck dissection was performed. Histopathological and immunochemical examinations were used to examine the SLN and all other lymph nodes. RESULTS: The preoperative SLN detection rate was 97.2% (35 of 36). SLN in level V were detected in four patients (11.1%). Metastases were found in 33.3% of the patients (12 of 36). All metastases were in the marked SLN. No skip metastases could be detected. A specificity of 100% and a sensitivity of 94.4% were identified for the SNB. CONCLUSION: The study confirms that SNB is a precise diagnostic procedure for assessing the nodal status of cervical lymph nodes. Further studies are needed to determine whether SNB without elective neck dissection for clinically and radiologically unremarkable cervical lymph nodes can become a reliable course of treatment for carcinomas of the head and neck region.

Synthesis, chemical behavior, structure elucidation and iNOS inhibitory activity of 1-substituted 3-methylsulfanyl-5,6,7,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazines.

Novel slim and shapely sp3-rich nitrogen containing heterocyclic ring systems are sought-after platforms for the expansion of molecular diversity in lead discovery. The present work describes the synthesis and characterization of a series of derivatives of hitherto unknown 3-methylsulfanyl-5,6,7,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazines 2. This approach was guided by a computational study, aiming at an optimization of previously reported [1,2,4]triazolo[1,2-a]pyridazine-1-thiones 1 known to inhibit the inducible nitric oxide synthase (iNOS). The title compounds are accessible by methylation of compounds 1 under mild conditions. The products were biologically evaluated by the same cell-based assay as applied for previous products of type 1 using RINm5F cells, which were stimulated to produce NO on the influence of proinflammatory cytokines IL-1ß and IFN-γ. Compounds 2 did not display the anticipated improved iNOS inhibitory activity in the selected assay but contribute to SAR in the field. In addition, an unprecedented formation of side-products 3 via oxidation has been investigated. The novel scaffolds represent attractive starting points for the construction of diverse molecules which differ considerably from known compounds based on flat and lipophilic aromatic scaffolds.

Implementation of a miniaturised navigation system in head and neck surgery for the detection and removal of foreign bodies.

The removal of embedded blast-generated fragments from soft tissue is very difficult, especially in the head and neck regions. First, because many retained foreign materials are non-metallic and can, therefore, not be detected by fluoroscopy, and second, because a broad exploration of the soft tissue is not possible in the facial area for functional and cosmetic reasons. Intraoperative navigation computer-assisted surgery (CAS) may facilitate the retrieval of foreign bodies and reduce exploration trauma. In a blind trial, five test specimens of different materials (glass, metal, wood, plastic, and stone) were inserted on the left and right sides of the head and neck of ten body donors through an intraoral incision. A second physician then detected and removed the foreign bodies from one side of the body without and from the other side of the body with navigation. We measured the duration of surgery, the extent of tissue trauma caused during surgery, the time it took to remove the foreign bodies, and the subjective evaluation of the usefulness of navigation. With the aid of the navigation system, the various foreign bodies were detected after an average of 26.7 (±35.1) s (p < 0.0001) and removed after an average of 79.1 (±66.2) s (p = 0.0239), with an average incision length of 10.0 (±3.5) mm. Without the navigation system, the foreign bodies were located after an average of 86.5 (±77.7) s and removed after an average of 74.1 (±45.9) s, with an average incision length of 13.0 mm (±3.6) mm (=0.0007). Intraoperative navigation systems are a valuable tool for removing foreign bodies from the soft tissue of the face and neck. Both the duration of surgery and the incision length can be reduced using navigation systems. Depending on the material of the foreign bodies and the signal intensity in the CT/MRI scanner, however, the detection reliability varies. All in all, navigation is considered to be a useful tool.

[Computer-aided reconstruction of the facial skeleton : Planning and implementation in clinical routine]. / Computerassistierte Gesichtsschädelrekonstruktion : Planung und Umsetzung in der klinischen Routine.

In computer-aided reconstruction of the facial skeleton, a workflow has been established involving the following steps: > diagnosis → planning and simulation → surgical procedure → validation and quality control <. In addition to clinical findings, the focus of diagnosis is on three-dimensional (3D) imaging, particularly computed tomography. Planning and simulation involves creation of a virtual model of the desired surgical outcome using special planning software. The accuracy of implant fit can be virtually verified before surgery. 3D models and virtual reconstructions can be used for manufacturing patient-specific implants. During the surgical procedure, planning must be transferred to the surgical site as accurately as possible. A number of techniques are available for this purpose, e. g., closed reduction, open reduction with the placement of anatomically preformed or patient-specific implants in combination with surgical guides, and the additional use of navigation. Validation and quality control require postprocedural 3D imaging. After reconstructions of the midface, 3D imaging should be performed even before surgery is completed. Malpositions can thus be directly corrected and unnecessary open reconstructions avoided. Mobile 3D c-arms are particularly useful for intraoperative 3D imaging. Whereas intraoperative imaging makes postoperative imaging after midface reconstruction unnecessary in many cases, postoperative 3D imaging in addition to intraoperative imaging may still be recommended after complex reconstructions of the facial skeleton.

Ceramic micro-injection molded nozzles for serial femtosecond crystallography sample delivery.

Serial femtosecond crystallography (SFX) using X-ray Free-Electron Lasers (XFELs) allows for room temperature protein structure determination without evidence of conventional radiation damage. In this method, a liquid suspension of protein microcrystals can be delivered to the X-ray beam in vacuum as a micro-jet, which replenishes the crystals at a rate that exceeds the current XFEL pulse repetition rate. Gas dynamic virtual nozzles produce the required micrometer-sized streams by the focusing action of a coaxial sheath gas and have been shown to be effective for SFX experiments. Here, we describe the design and characterization of such nozzles assembled from ceramic micro-injection molded outer gas-focusing capillaries. Trends of the emitted jet diameter and jet length as a function of supplied liquid and gas flow rates are measured by a fast imaging system. The observed trends are explained by derived relationships considering choked gas flow and liquid flow conservation. Finally, the performance of these nozzles in a SFX experiment is presented, including an analysis of the observed background.

Fast in situ phase and stress analysis during laser surface treatment: a synchrotron x-ray diffraction approach.

An in situ stress analysis by means of synchrotron x-ray diffraction was carried out during laser surface hardening of steel. A single exposure set-up that based on a special arrangement of two fast silicon strip line detectors was established, allowing for fast stress analysis according to the sin(2)ψ x-ray analysis method. For the in situ experiments a process chamber was designed and manufactured, which is described in detail. First measurements were carried out at the HZG undulator imaging beamline (IBL, beamline P05) at the synchrotron storage ring PETRA III, DESY, Hamburg (Germany). The laser processing was carried out using a 6 kW high power diode laser system. Two different laser optics were compared, a Gaussian optic with a focus spot of ø 3 mm and a homogenizing optic with a rectangular spot dimension of 8 × 8 mm(2). The laser processing was carried out using spot hardening at a heating-/cooling rate of 1000 K/s and was controlled via pyrometric temperature measurement using a control temperature of 1150 °C. The set-up being established during the measuring campaign allowed for this first realization data collection rates of 10Hz. The data evaluation procedure applied enables the separation of thermal from elastic strains and gains unprecedented insight into the laser hardening process.

[The hybrid operating room. Home of high-end intraoperative imaging]. / Der Hybridoperationssaal. Zentrum intraoperativer Bildgebung.

A hybrid operating room must serve the medical needs of different highly specialized disciplines. It integrates interventional techniques for cardiovascular procedures and allows operations in the field of orthopaedic surgery, neurosurgery and maxillofacial surgery. The integration of all steps such as planning, documentation and the procedure itself saves time and precious resources. The best available imaging devices and user interfaces reduce the need for extensive personnel in the OR and facilitate new minimally invasive procedures. The immediate possibility of postoperative control images in CT-like quality enables the surgeon to react to problems during the same procedure without the need for later revision.

[Computer-assisted reconstruction of the facial skeleton]. / Die computergestützte Gesichtsschädelrekonstruktion.

Injury to the facial skeleton may result not only in aesthetic but also functional deficits. Computer-assisted surgery promises predictable reconstructive results. In clinical routine the authors use the combination of preoperative planning, intraoperative navigation and intraoperative imaging to treat complex facial trauma. With preoperative planning the intended reconstructive results can be precisely preplanned and guided intraoperatively using navigational surgery. Intraoperative imaging achieves the final intraoperative validation. Using computer-assisted surgery dislocation and malformation of fragments and transplants can be avoided in facial reconstruction. This means reliable quality control of surgical outcome and the number of further surgeries can be reduced in this complex reconstructive surgery.

Marker-based introduction of three quantitative-trait loci conferring resistance to Fusarium head blight into an independent elite winter wheat breeding population.

Fusarium head blight (FHB) is one of the most important wheat diseases that causes yield and quality losses as well as contamination with deoxynivalenol (DON). This study aimed for marker-based introduction of three previously mapped QTLs from two German winter wheat resistance sources into an elite background unrelated to the mapping population. A double cross (DC) served as initial population that combined two resistance donor-QTL alleles from "Dream" (Qfhs.lfl-6AL, Qfhs.lfl-7BS) and one donor-QTL allele from "G16-92" on chromosome 2BL with two high yielding, susceptible elite winter wheats ("Brando", "LP235.1"). The initial population of 600 DC-derived F(1) lines was selected with SSR markers for the respective QTLs. After two marker-selection steps, each of eight marker classes was represented by 9-22 lines possessing the respective donor-QTL allele or all possible combinations thereof in the homozygous state. The effect of the QTLs was estimated by field tests at four locations inoculated with Fusarium culmorum. Resistance was measured as the mean of multiple FHB ratings (0-100%). Marker classes incorporating only one QTL were not significantly more resistant than the class without any QTL, the combination of two donor-QTL alleles reduced FHB significantly. On average, lines with Qfhs.lfl-6AL were significantly taller than lines without this QTL. A considerable variation for FHB resistance was found in all marker classes. Marker-based introduction of two QTLs enhanced mean FHB rating by about 40 percentage points, the selected plants, however, were, on average, significantly taller. Both findings strongly support a phenotypic selection following after marker-based introduction of effective QTLs.

REML approach for adjusting the Fusarium head blight rating to a phenological date in inoculated selection experiments of wheat.

Fusarium head blight is one of the most important wheat diseases causing grain yield and quality losses as well as mycotoxin contamination all over the world. Since Fusarium cannot be reliably controlled with fungicides, breeding has become a favorable tool to decrease the infection severity. In most cases, selection for Fusarium resistance is done by artificial infection in the field. However, there is a risk in preferring late heading genotypes, because heading of wheat is negatively correlated to head blight severity. Because an indirect selection for late maturity is not intended, we considered a statistical approach to avoid this problem. In this paper, we propose a mixed model to analyze extensive Fusarium head blight rating in resistance breeding experiments of wheat. The objective of the analysis was to select for Fusarium resistance, while at the same time ensuring that late heading genotypes, which show less head blight over the shorter vegetation period, are not preferred. Thus, selection was to be done such that genetic variability for heading date was retained. Therefore, the statistical model contained a covariate to adjust for differences in the heading date. The use of covariate adjustment is an easily handled alternative to a bivariate analysis. Covariate adjustment will in practice often work almost equally well as bivariate analysis. Any statistical software with powerful mixed model analysis tools can be used for this type of analysis. We propose an ad hoc method to obtain heritability estimates and a form of LSD (least significance difference) as a measure of accuracy on the basis of the proposed model and under special consideration of the experimental design. The ad hoc LSD was used as a rough measure to judge rankings of genotypic means (BLUPs). Friedman's super smoother was used to compare smoothed rank estimates for adjusted and unadjusted genotypes against increasing smoothed heading dates. Traits were transformed to meet the model assumptions, especially homogeneity of errors and normality, and back-transformation of means and standard errors was conducted by using the delta method.

Immunoglobulin and free light chain abnormalities in Gaucher disease type I: data from an adult cohort of 63 patients and review of the literature.

Gaucher disease type I, the most common lysosomal storage disorder, is associated with immunoglobulin abnormalities. We studied the prevalence, risk factors, pathogenesis, and effect of enzyme relation therapy (ERT) on gammopathies in an adult Gaucher disease type I cohort (N = 63) and related the results to a review of the currently available literature. Polyclonal gammopathies and monoclonal gammopathy of undetermined significance (MGUS) in our adult GD I cohort were found in 41% and 19% of patients. These results are similar to the data from the literature and correspond to the increased risk of multiple myeloma (MM) that has been described. The prevalence of MGUS in our cohort increased with age but was not associated with disease severity or exposure time. The serum levels of free light chains of immunoglobulins were measured and were not found predictive for the development of MGUS or MM. Levels of pro- as well as anti-inflammatory cytokines, growth factors, and chemokines, especially those involved in inflammation and B-cell function, are disturbed in GD I, with the most impressive and consisting elevations for interleukin-10 and pulmonary and activation-regulated chemokine. A beneficial effect of ERT on the occurrence and progression of gammopathies was suggested from longitudinal data.

Stacking quantitative trait loci (QTL) for Fusarium head blight resistance from non-adapted sources in an European elite spring wheat background and assessing their effects on deoxynivalenol (DON) content and disease severity.

Fusarium head blight (FHB) is a devastating disease in wheat that reduces grain yield, grain quality and contaminates the harvest with deoxynivalenol (DON). As potent resistance sources Sumai 3 and its descendants from China and Frontana from Brazil had been analysed by quantitative trait loci (QTL) mapping. We introgressed and stacked two donor QTL from CM82036 (Sumai 3/Thornbird) located on chromosomes 3B and 5A and one donor QTL from Frontana on chromosome 3A in elite European spring wheat and estimated the effects of the three individual donor QTL and their four combinations on DON, Fusarium exoantigen content, and FHB rating adjusted to heading date. One class with the susceptible QTL alleles served as control. Each of the eight QTL classes was represented by 12-15 F(3)-derived lines tested in F(5) generation as bulked progeny possessing the respective marker alleles homozygously. Traits were evaluated in a field experiment across four locations with spray inoculation of Fusarium culmorum. All three individual donor-QTL alleles significantly reduced DON content and FHB severity compared to the marker class with no donor QTL. The only exception was the donor-QTL allele 3A that had a low, but non-significant effect on FHB severity. The highest effect had the stacked donor-QTL alleles 3B and 5A for both traits. They jointly reduced DON content by 78% and FHB rating by 55% compared to the susceptible QTL class. Analysis of Fusarium exoantigen content illustrates that lower disease severity is associated with less mycelium content in the grain. In conclusion, QTL from non-adapted sources could be verified in a genetic background of German elite spring wheat. Within the QTL classes significant (P<0.05) genotypic differences were found among the individual genotypes. An additional phenotypic selection would, therefore, be advantageous after performing a marker-based selection.

[Hemangiopericytoma (extrapleural solitary fibrous tumour). Exemplified and discussed on the basis of two cases]. / Hämangioperizytom (extrapleuraler solitärer fibröser Tumor). Dargestellt und diskutiert anhand zweier Patientenbeispiele.

BACKGROUND: Hemangiopericytoma was first mentioned in 1942. It is a very uncommon potentially malignant vascular tumour which can occur at every site of the body. According to the WHO, most of the tumours formerly diagnosed as hemangiopericytomas are considered to be extrapleural solitary fibrous tumours. The diagnosis of "hemangiopericytoma" is now only determined if a constant histological picture of hemangiopericytoma is present. The tumour can lead to lymphogenous or hematogenous metastasis. The major location of occurrence is the cutis and subcutis. It originates from the pericytes of the vascular wall. This is reflected in its vascular character and therefore the hemangiopericytoma might clinically be mistaken for a hemangioma. CASE REPORTS: Patient 1: 60 years, female; diagnosis: malignant suboccipital hemangiopericytoma; size: 4.9 x 4.5 x 4.2 cm; pT1bNXMX L0 V0 Pn0; stage IA; grading G1; R0.Patient 2: 38 years, male; diagnosis: benign hemangiopericytoma infraorbital left; size 1.5 x 1.5 x 1.5 cm. DISCUSSION: Most often the hemangiopericytoma becomes clinically conspicuous as a slowly growing, painless swelling. The consistency ranges from soft to dense, and the color is greyish-blue. The slow and painless growth carries the danger of a clinically wrong diagnosis and thus delayed therapy. The histological diagnosis of hemangiopericytoma is determined by biopsy. Besides histology, MRI and angiography are methods that can be employed to diagnose hemangiopericytoma. The therapy of choice is the complete tumour-resection with a safety margin of 1 cm. In the case of an aggressive growth pattern, adjuvant postoperative radiotherapy is recommended. Until now there has been no documented specific therapy concept for managing incomplete resection and the occurrence of metastasis. There are reports about chemo- and radiotherapy either on their own or combined which evidence differing degrees of success. Lifelong monitoring is necessary because recrudescences and metastases can occur even decades later.

Frontalis suspension combined with blepharoplasty as an effective treatment for blepharospasm associated with apraxia of eyelid opening.

PURPOSE: Essential blepharospasm can be associated with apraxia of eyelid opening and is characterized by the inability to initiate the act of eyelid elevation even after cessation of orbicularis spasms. Current therapies such as botulinum toxin injections, orbicularis resection, or neurectomy may be unsuccessful or have undesired side effects. METHODS: Frontalis suspension was used to treat 13 consecutive patients with apraxia and blepharospasm during a 4-year interval. Follow-up ranged from 16 months to 55 months. To improve the aesthetic outcome, an upper blepharoplasty was done at the same time as the frontalis suspension in 7 cases. RESULTS: Good or excellent functional results were obtained in 10 of 13 patients. In 6 of these patients, the spasm disappeared completely. Therapy was unsuccessful in 1 patient, and in 2 patients blepharospasm recurred after 9 months. CONCLUSION: Patients with blepharospasm and apraxia of eyelid opening may benefit from a frontalis suspension operation, which can be considered minimally invasive and reversible.

Processing of artificial peptide-DNA-conjugates by the mitochondrial intermediate peptidase (MIP).

Import of DNA from the cytoplasm into the mitochondrial matrix is an obligatory step for an in organello site-directed mutagenesis or gene therapy approach on mitochondrial DNA diseases. In this context, we have developed an artificial DNA translocation vector that is composed of the mitochondrial signal peptide of the ornithine transcarbamylase (OTC) and a DNA moiety. While this vector is capable of directing attached passenger molecules to the mitochondrial matrix, the recognition of this artificial molecule by the endogenous mitochondrial signal peptide processing machinery as well as the cleavage of the peptide plays a pivotal role in the release of the attached DNA. To study the proteolytic processing of the artificial vector, various signal peptide-DNA-conjugates were treated with purified mitochondrial intermediate peptidase. When the leader peptide is directly linked to the DNA moiety without an intervening spacer, MIP processing is prevented. Cleavage of the peptide can be restored, however, when the first ten amino acid residues of the mature part of OTC are appended at the carboxy-terminal end of the signal peptide. Our results show that artificial peptide-DNA-conjugates are recognized by the mitochondrial proteolytic machinery, and therefore an interference of the peptide with the DNA function can be excluded.

Dynamic relocation of chromosomal protein HMG-17 in the nucleus is dependent on transcriptional activity.

Chromosomal proteins HMG-14/-17 are nucleosomal binding proteins, which alter the structure of the chromatin fiber and enhance transcription, but only from chromatin templates. Here we show that in tissue culture cells, HMG-17 protein colocalizes with sites of active transcription. Incubation of permeabilized cells with a peptide corresponding to the nucleosomal binding domains of HMG-14/-17 specifically arrested polymerase II-dependent transcription. In these cells the peptide displaces HMG-17 from chromatin and reduces the cellular content of the protein. These results suggest that the presence of HMG-14/-17 in chromatin is required for efficient polymerase II transcription. In non-permeabilized, actively transcribing cells, the protein is dispersed in a punctate pattern, throughout the nucleus. Upon transcriptional inhibition by alpha-amanitin or actinomycin D, the protein gradually redistributes until it localizes fully to interchromatin granule clusters, together with the splicing factor SC35. The results suggest that the association of HMG-17 with chromatin is dynamic rather than static, and that in the absence of transcription, HMG-17 is released from chromatin and accumulates in interchromatin granule clusters. Thus, the intranuclear distribution of chromosomal proteins which act as architectural elements of chromatin structure may be dynamic and functionally related to the transcriptional activity of the cell.