MucR protein: Three decades of studies have led to the identification of a new H-NS-like protein.

MucR belongs to a large protein family whose members regulate the expression of virulence and symbiosis genes in α-proteobacteria species. This protein and its homologs were initially studied as classical transcriptional regulators mostly involved in repression of target genes by binding their promoters. Very recent studies have led to the classification of MucR as a new type of Histone-like Nucleoid Structuring (H-NS) protein. Thus this review is an effort to put together a complete and unifying story demonstrating how genetic and biochemical findings on MucR suggested that this protein is not a classical transcriptional regulator, but functions as a novel type of H-NS-like protein, which binds AT-rich regions of genomic DNA and regulates gene expression.

1-km resolution rebound surfaces and paleotopography of glaciated North America since the Last Glacial Maximum.

We present a series of 1-km spatial resolution rebound (isobase) surfaces based on publicly distributed predictions obtained from the glacio-isostatic adjustment models known as ICE-5G (VM2 L90), ICE-6G_C (VM5a) and ICE-7G_NA (VM7). Our objective is to provide readily accessible tools for a broad range of geological and paleoenvironmental studies, and to facilitate direct comparison between models' predictions and field-based observations. Rebound surfaces were interpolated at the scale of North American ice sheets (35.5°-89.5°N; 45°-165°W) and for each time increment of the models (1,000-500 yrs, between 26,000-21,000 yrs BP and present-day). The assessment of the interpolations indicates that the rebound surfaces have an overall vertical accuracy of ∼0.4 m compared to original ICE-xG outputs. These rebound surfaces were combined with the GEBCO 2021 present-day elevation grid to reconstruct the paleotopography for each time increment of the models and are all presented as raster files that can be easily integrated into geographical information systems. The resulting datasets therefore provide a unique support for geological, paleoenvironmental and archeological studies.

Identifying the region responsible for Brucella abortus MucR higher-order oligomer formation and examining its role in gene regulation.

MucR is a member of the Ros/MucR family of prokaryotic zinc-finger proteins found in the α-proteobacteria which regulate the expression of genes required for the successful pathogenic and symbiotic interactions of these bacteria with the eukaryotic hosts. The structure and function of their distinctive zinc-finger domain has been well-studied, but only recently the quaternary structure of the full length proteins was investigated demonstrating their ability to form higher-order oligomers. The aim of this study was to identify the region of MucR involved in higher-order oligomer formation by analysing deletion and point mutants of this protein by Light Scattering, and to determine the role that MucR oligomerization plays in the regulatory function of this protein. Here we demonstrate that a conserved hydrophobic region at the N-terminus of MucR is responsible for higher-order oligomer formation and that MucR oligomerization is essential for its regulatory function in Brucella. All these features of MucR are shared by the histone-like nucleoid structuring protein, (H-NS), leading us to propose that the prokaryotic zinc-finger proteins in the MucR/Ros family control gene expression employing a mechanism similar to that used by the H-NS proteins, rather than working as classical transcriptional regulators.

MucR binds multiple target sites in the promoter of its own gene and is a heat-stable protein: Is MucR a H-NS-like protein?

The protein MucR from Brucella spp. is involved in the expression regulation of genes necessary for host interaction and infection. MucR is a member of the Ros/MucR family, which comprises prokaryotic zinc-finger proteins and includes Ros from Agrobacterium tumefaciens and the Ml proteins from Mesorhizobium loti. MucR from Brucella spp. can regulate the expression of virulence genes and repress its own gene expression. Despite the well-known role played by MucR in the repression of its own gene, no target sequence has yet been identified in the mucR promoter gene. In this study, we provide the first evidence that MucR from Brucella abortus binds more than one target site in the promoter region of its own gene, suggesting a molecular mechanism by which this protein represses its own expression. Furthermore, a circular dichroism analysis reveals that MucR is a heat-stable protein. Overall, the results of this study suggest that MucR might resemble a H-NS protein.

Validation of the Dépistage Cognitif de Québec: A New Cognitive Screening Tool for Atypical Dementias.

OBJECTIVE: This study aimed to validate and provide normative data for the Dépistage Cognitif de Québec (DCQ; www.dcqtest.org), a new cognitive screening tool for atypical dementias. METHOD: The DCQ was developed by expert behavioral neurologists and clinical neuropsychologists based on updated criteria for Alzheimer's disease, primary progressive aphasia, and behavioral variant frontotemporal dementia. It targets five relevant domains: Memory, Visuospatial, Executive, Language, and Behavior. Validation was performed in a population-based sample of 410 healthy French-speaking Canadians aged between 50 and 89 years old. Normative data were derived from a subsample of 285 participants. RESULTS: Mean DCQ total score (out of 100) was 89.17 (SD = 7.36). Pearson's correlation coefficient showed a strong and significant correlation (r = .71, p < .001) with the Montreal Cognitive Assessment. Internal consistency for the cognitive domains assessed by Cronbach's alpha was satisfactory (.74). Test-retest reliability was adequate (Pearson's coefficient = . 70, p < .001) and interrater reliability, excellent (intraclass correlation = .99, p < .001). Normative data shown in percentiles were stratified by age and education. CONCLUSIONS: This study suggests that the DCQ is a valid and reliable cognitive screening test. Application of the DCQ on populations with atypical dementias is underway to derive sensitivity and specificity values for various dementias.

Ml proteins from Mesorhizobium loti and MucR from Brucella abortus: an AT-rich core DNA-target site and oligomerization ability.

Mesorhizobium loti contains ten genes coding for proteins sharing high amino acid sequence identity with members of the Ros/MucR transcription factor family. Five of these Ros/MucR family members from Mesorhizobium loti (Ml proteins) have been recently structurally and functionally characterized demonstrating that Ml proteins are DNA-binding proteins. However, the DNA-binding studies were performed using the Ros DNA-binding site with the Ml proteins. Currently, there is no evidence as to when the Ml proteins are expressed during the Mesorhizobium lo ti life cycle as well as no information concerning their natural DNA-binding site. In this study, we examine the ml genes expression profile in Mesorhizobium loti and show that ml1, ml2, ml3 and ml5 are expressed during planktonic growth and in biofilms. DNA-binding experiments show that the Ml proteins studied bind a conserved AT-rich site in the promoter region of the exoY gene from Mesorhizobium loti and that the proteins make important contacts with the minor groove of DNA. Moreover, we demonstrate that the Ml proteins studied form higher-order oligomers through their N-terminal region and that the same AT-rich site is recognized by MucR from Brucella abortus using a similar mechanism involving contacts with the minor groove of DNA and oligomerization.

Bilateral stereotactic anterior capsulotomy for obsessive-compulsive disorder: long-term follow-up.

BACKGROUND AND PURPOSE: Psychosurgery, such as anterior capsulotomy, is a therapeutic option for treatment-resistant obsessive-compulsive disorder (OCD). In this paper, we present a prospective, long-term follow-up study aimed at evaluating both the efficacy and the safety of anterior capsulotomy for the treatment of severe, refractory OCD. METHODS: Twenty-four patients were surgically treated in our centre between 1997 and 2009, 19 of whom were included in this study. Patients were assessed at 3, 6, 12, and 24 months and last follow-up (mean of 7 years) was carried out by phone. OCD symptom severity was evaluated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A patient with an improvement rate of over 35% in the Y-BOCS score was considered a responder, while a patient with a 25% improvement was considered a partial responder. RESULTS: With a mean improvement of 31% in the Y-BOCS score at long-term follow-up, 36.8% of the patients responded fully to the procedure and 10.5% were considered partial responders, for an overall response rate of 47.3% of patients. At the end of the study, 3/19 patients had recovered (Y-BOCS score <8) and 3/19 were in remission (Y-BOCS score <16). No cases of mortality were reported and the overall adverse event rate was 57.9%. Only 2 patients had permanent surgical complications. CONCLUSIONS: Anterior capsulotomy is an effective and safe technique for the treatment of severe refractory OCD in patients who have no other alternative to improve their symptoms.

Time perception disorders are related to working memory impairment in schizophrenia.

Time perception (TP) impairment in schizophrenia has been originally described by clinicians and afterwards addressed in laboratory. Previous studies generally observed that schizophrenia patients overestimate time and that their timing sensitivity is impaired. However, because of the disease cognitive impairments, no study until now allows to draw definitive conclusions about the nature of TP disturbances. The aim of this study is to isolate a genuine TP disorder in schizophrenia, i.e., a disorder that would be related to the functioning of an internal clock. The main hypothesis tested is that patients' internal clock runs faster than that of healthy controls. Twenty-five patients suffering from a first-episode of schizophrenia and twenty-five healthy controls performed an innovative task called method of dynamic stimuli, designed to measure the natural frequency (F(n)) of the internal clock, concomitant with a neuropsychological assessment. We observed no significant difference in F(n) between groups. Compared to controls, there was a marginally higher variability in time reproduction in patients. Patients' pattern of results and significant correlations between TP tasks and memory outcomes suggest that TP impairments are related to memory impairment in schizophrenia. These conclusions are supported by a growing literature showing that cognition is involved in TP in schizophrenia.

Potentially curative radiotherapy for non-small-cell lung cancer in Norway: a population-based study of survival.

PURPOSE: The efficacy of curative irradiation in the treatment of non-small-cell lung cancer patients is considered limited. The purpose of this study was to evaluate long-term survival in a population-based approach. METHODS AND MATERIALS: Cases of non-small-cell lung cancer diagnosed from 1993 to 2001 were identified in the Cancer Registry of Norway. Electronic linkage with national data from the hospitals' radiotherapy verification systems identified those who received potentially curative doses (≥ 50 Gy). Hospital records were reviewed for all patients. RESULTS: A total of 497 patients (336 men) were identified with a radiation dose of ≥ 50 Gy delivered to the lung region. Of these, 41% received 60 Gy or more. The majority (70%) of patients included had advanced stage disease: 24% Stage IIIA and 46% Stage IIIB. The overall 1-, 3-, and 5-year observed survival rates were 53%, 16%, and 9%, respectively. Multivariable analyses identified stage and chemotherapy, but not radiation dose, as significant independent prognostic variables for survival. However, 68% of patients treated with chemotherapy participated in prospective studies with inclusion criteria that excluded patients with less favorable prognostic factors, leading to a selection bias. The number of fractions and the radiation doses varied widely among different hospitals. CONCLUSION: The long-term prognosis after radiation therapy is poor. More sophisticated, targeted, and uniform delivery of radiation therapy is needed. The apparent benefit of chemotherapy may in part be due to selection of patients with more favorable prognostic factors for this therapy.

Medial prefrontal cortex activity during memory encoding of pictures and its relation to symptomatic improvement after citalopram treatment in patients with major depression.

BACKGROUND: Brain imaging studies of major depressive disorder have shown alterations in the brain regions typically involved in episodic memory, including the prefrontal cortex and medial temporal areas. Some studies of major depressive disorder have linked episodic memory performance to treatment response. In this study, we sought to identify brain regions whose activity, measured during the encoding of pictures, predicted symptomatic improvement after 8 weeks of citalopram treatment. METHODS: We included 20 unmedicated depressed patients. These patients performed an episodic recognition memory task during functional magnetic resonance imaging. During the encoding phase, 150 pictures depicting emotionally positive, negative or neutral content were presented, and the participants were required to classify each picture according to its emotional valence. The same 150 pictures were presented, along with 150 new ones, for a recognition task. We asked participants to distinguish the old pictures from the new ones. We assessed symptom severity by use of the 21-item Hamilton Rating Scale for Depression (HAM-D) at baseline and after 8 weeks of citalopram treatment. We performed subsequent memory effect analyses using SPM2 software. We explored the relation between brain activation during successful encoding of pictures and symptomatic improvement. RESULTS: Patients showed a mean symptomatic improvement of 54.5% on the HAM-D after 8 weeks. Symptomatic improvement was significantly and positively correlated with picture recognition memory accuracy. We also found that the activity of the ventromedial prefrontal cortex and anterior cingulate cortex during successful encoding was significantly correlated with symptomatic improvement. Finally, we found greater activation in the ventromedial prefrontal cortex during the successful encoding of positive pictures in comparison with neutral pictures. LIMITATIONS: During the recognition memory task, 5 participants (among the best responders to treatment) were not included in the valence-specific analyses because they had very few errors. A more challenging task would have allowed the inclusion of most patients. CONCLUSION: Different types of functional imaging paradigms have been used to explore whether the activity of specific brain regions measured at baseline is predictive of a better response to treatment in major depressive disorder. Among these regions, the medial prefrontal cortex and anterior cingulate cortex usually show the strongest predictive value. According to our results, the medial prefrontal cortex and anterior cingulate cortex could have an effect on treatment response in major depressive disorder by contributing to the successful encoding of positively valenced information.

Platelet-Derived Growth Factors in Non-GIST Soft-Tissue Sarcomas Identify a Subgroup of Patients with Wide Resection Margins and Poor Disease-Specific Survival.

Background. Optimal treatment of nongastrointestinal stromal tumor soft-tissue sarcomas (non-GIST STSs) is resection with wide margins. This study investigates the prognostic impact of the angiogenesis-associated platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) in non-GIST STS patients with wide and nonwide resection margins. Method. Tumor samples and clinical data from 249 patients with non-GIST STS were obtained, and tissue microarrays were constructed for each specimen. Immunohistochemistry was used to evaluate the expression of PDGF-A, -B, -C, and -D and PDGFR-α and -ß. Results. In the multivariate analysis of patients with wide resection margins, high expression of PDGF-B (P = .013, HR = 2.954, and 95% CI = 1.255-6.956) and the coexpression of PDGF-B and PDGFR-α (overall; P = .016, high-low/low-high; P = .051, HR = 2.678, 95% CI = 0.996-7.200, high/high; P = .004, HR = 3.930, 95% CI = 1.542-10.015) were independent negative prognostic markers for disease-specific survival. Conclusion. PDGF-B and the coexpression of PDGF-B and PDGFR-α are strong and independent prognostic factors in non-GIST STSs with wide resection margins.

The structure of sensory events and the accuracy of time judgments.

We investigated how does the structure of empty time intervals influence temporal processing. In experiment 1, the intervals to be discriminated were the silent durations marked by two sensory signals, both lasting 10 or 500 ms; these signals were two identical flashes (intramodal: VV), or one visual flash (V) followed by an auditory tone (A) (intermodal: VA). For the range of duration under investigation (standards = 0.2, 0.6, 1, or 1.4 s), the results indicated that both the marker length and sensory mode influenced discrimination, but no interaction between these variables or between one of these variables and standard duration was significant. In experiment 2, we compared, for each of four marker-type conditions (VV, AA, VA, AV; and standard = 1 s), intervals marked by two 10 ms signals with intervals marked by unequal signal length (markers 1 and 2 lasting 10 and 500 ms, or 500 and 10 ms). As in experiment 1, the results revealed significant marker-mode and marker-length effects, but no significant interaction between these variables. Experiment 3 showed that, for the same conditions as in experiment 2, perceived duration is not influenced by marker length and that the variability of interval reproductions does not depend on the perceived duration of intervals. The results are discussed in the light of a single-clock hypothesis: marker-length and marker-mode effects are presented as being non-temporal sources of variability associated mainly with sensory and memory processes.

Allelic loss at the GPx-1 locus in cancer of the head and neck.

Glutathione peroxidase is a selenium-containing, antioxidant enzyme previously implicated in the risk and development of lung and breast cancer, in part the result of allelic loss at the GPx-1 locus. This study examined allelic loss at the same locus in squamous cell carcinomas of the head and neck. The frequency of a polymorphism at codon 198 resulting in either a leucine or a proline at that position was surveyed by comparing 133 DNA samples obtained from head and neck tumors and 517 samples obtained from cancer-free individuals. Tumor DNAs exhibited fewer pro/leu heterozygotes as compared to DNA obtained from the cancer-free population. Fewer GPx-1 heterozygotes were verified by determining the frequency of highly polymorphic alanine repeat sequences in the same gene. The analysis revealed an approximately 42% reduction in heterozygosity in the DNA from the tumor samples. In order to assess loss of heterozygosity (LOH) at the GPx-1 locus, DNA was genotyped from peripheral lymphocytes, tumor tissue, and microscopically normal tissues adjacent to the tumor, derived from the same patients. These studies indicated LOH at the GPx-1 locus in each of the three tumor/normal tissues sample sets examined. Furthermore, LOH in the microscopically normal tissues at the tumor margin occurred in two of the three sample sets examined. These data implicate GPx-1 in the development of squamous cell carcinoma the head and neck and suggest that allelic loss of this gene, or one tightly linked to it, is an early event in the development of this type of malignancy.