Interestingly, a temporal relationship between stressful

Interestingly, a temporal relationship between stressful selleck life events and disease onset is relevant only to pituitary-dependent Cushing’s disease, and not to the pituitary-independent forms. A number of psychiatric and psychological disturbances may be associated with the active hypercortisolemic state, regardless of its etiology. Within the high frequency of mood

disorders (about 60%), major depression is the most common complication. Other psychopathological aspects include mania, anxiety disorders, psychological symptoms (demoralization, irritable mood, somatization) and cognitive impairment. Cognitive symptoms are associated with brain abnormalities (mainly loss of brain volume). Quality of life may be seriously compromised during both active and post-treatment phases. Long-standing hypercortisolism may imply a degree of irreversibility of the pathological process. Recovery, thus, may be delayed and be influenced by highly individualized affective responses. Outcomes of Cushing’s syndrome treatment are not fully satisfactory. Within its great complexity, a conceptual shift

from a merely biomedical care to a psychosomatic consideration of the person and his/her quality of life appears to be necessary to improve effectiveness. It is time to translate the research evidence that has accumulated into clinical PD0325901 manufacturer practice initiatives. To patients who show persistence or even worsening of psychological distress upon adequate endocrine treatment psychiatric/psychological interventions should be readily available. Applying interdisciplinary expertise and addressing the needs for rehabilitation would markedly improve final outcome.”
“Practicing and perfecting the art of medicine demands recognition that uncertainty permeates all clinical decisions. When delivering clinical care, clinicians face a multiplicity of potential diagnoses, limitations

SB203580 manufacturer in diagnostic capacity, and “”sub-clinical”" disease identified by tests rather than by clinical manifestations. In addition, clinicians must recognize the rapid changes in scientific knowledge needed to guide decisions. Cushing’s syndrome is one of several disorders in which there may be considerable difficulty and delay in diagnosis. This article describes a current model of clinical reasoning, some of its challenges, and the application of the principles of clinical epidemiology to meet some of those challenges.”
“Ectopic Cushing’s syndrome usually relates to the ectopic ACTH syndrome (EAS) and represents similar to 20% of ACTH-dependent and similar to 10% of all types of Cushing’s syndrome (CS). Nearly any neuroendocrine or non-endocrine tumours may be associated with EAS, but the more prevalent tumours are bronchial carcinoids, small cell lung carcinomas, pancreatic carcinoids, thymic carcinoids, medullary carcinomas of the thyroid, and phaeochromocytomas.

“The incidence of postoperative complications in cleft car

“The incidence of postoperative complications in cleft care is low. In this 19-year retrospective analysis of cleft lip and palate patients treated with preoperative nasoalveolar molding, we examine the incidence of postoperative oronasal fistulae. The charts of 178 patients who underwent preoperative nasoalveolar molding by the same orthodontist/prosthodontist team and primary cleft lip/palate repair by the same surgeon over a 19-year period were reviewed. Millard, Mohler, Cutting, or Mulliken-type techniques

were used for cleft lip repairs. Oxford-, Bardach-, or von Langenbeck-type techniques were used for cleft palate repairs. One nasolabial fistula occurred after primary cleft lip repair (0.56% SP600125 order incidence) and was repaired surgically. Four palatal fistulae (3 at the junction between soft and hard palate and 1 at the right anterior palate near the incisive foramen) occurred, but 3 healed spontaneously. Only 1 palatal fistula (0.71%) required surgical repair. All 5 fistulae occurred within the first 8 years of the study period, with 4 (80%) of 5 occurring within the first 3 years. Although fistula rate may be related to surgeon experience Selleckchem Fer-1 and the evolution of presurgical techniques, nasoalveolar molding in conjunction with nasal floor closure contributes to a low incidence

of oronasal fistulae.”
“Spanish medical graduates who apply for a medical specialty training position (MIR) must take an examination that will shape their future personal and professional lives. Preparation for the test represents an important stressor that persists for several months. The aim of this study was to elucidate GSK 4529 the stress pattern of this group and evaluate possible changes in the circadian rhythm of cortisol release in medical graduates preparing for this test. A repeated-measures longitudinal study was performed, measuring the salivary cortisol concentrations in 36 medical graduates (13 males and 23 females; mean age of 24.2 years) on five sampling

days. Five cortisol samples were collected from 07: 00 to 21: 00 h in order to monitor changes in the circadian rhythm. On all sampling days (except on the day of the official examination), anxiety and psychological stress were evaluated with the Spanish versions of the State-Trait Anxiety Inventory (STAI) and the Perceived Stress Scale (PSS). During the study period, participants showed higher levels of anxiety than the Spanish reference population as well as a progressive increase in self-perceived stress. A significant increase in salivary cortisol concentration was observed in both chronic (study and examination preparation) and acute (examinations) situations. Our results suggest that the cortisol awakening response (CAR) may be a good indicator of anticipatory stress but is unaffected by long-term examination preparation.

The promoter region of SPT was dissected by truncation and deleti

The promoter region of SPT was dissected by truncation and deletion, and two main regions occupied by tissue-specific enhancers were identified. These were correlated with eight regions conserved between promoter regions of Arabidopsis, Brassica oleracea, and Brassica rapa. When transformed into Arabidopsis, the B. oleracea promoter

drove expression in reproductive tissues mostly comparable to the 7-Cl-O-Nec1 equivalent Arabidopsis promoter. There is genetic evidence that SPT function in the gynoecium is associated with the perception of auxin. However, site-directed mutagenesis of three putative auxin-response elements had no detectable effect on SPT expression patterns. Even so, disruption of a putative E-box variant adjacent to one of these resulted in a loss of valve dehiscence buy Citarinostat zone expression. This expression was also specifically lost in mutants of another bHLH gene INDEHISCENT, indicating that IND may directly regulate SPT expression through this variant E-box.”
“We modified synthetic isoprene rubber by means of the in situ generation of silica particles through the sol-gel process starting from tetraethoxysilane (TEOS) as an inorganic oxide precursor. Different reaction conditions were investigated with variations in the initial TEOS content, the reaction time of the sol-gel process, and the presence of a coupling/surfactant agent (octyltriethoxysilane). Organic-inorganic hybrid materials

with a silica content up to 70 phr were obtained with the complete conversion of TEOS to silica for a long enough sol-gel reaction time. A very homogeneous dispersion of silica particles was observed in all cases together with a very good adhesion between the filler and matrix. The size of the in situ generated silica was controlled by the appropriate addition of octyltriethoxysilane. Swelling and extraction tests and dynamic mechanical analysis indicated that the vulcanization process of isoprene rubber was perturbed by

the sol-gel process; this led to a slight decrease in the crosslinking degree. However, a significant reinforcing selleck chemical effect due to the presence of silica particles was observed for all of the investigated samples. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 3422-3428, 2011″
“Spatial filtering is demonstrated at beam-type excitations by utilizing finite thickness slabs of two-dimensional dielectric photonic crystals (PCs) showing exotic Fabry-Perot resonances that are preserved over a wide range of variation of the incidence angle. Bandstop and dual-bandpass filtering effects are illustrated theoretically and the corresponding filters are validated in the microwave experiments by using square-lattice PCs. It is shown that the basic transmission features that were observed earlier for a plane-wave illumination are also recognizable at beam-type excitations. The proposed spatial filtering mechanism exhibits directional beaming.

(C) 2009 American Institute of Physics [DOI: 10 1063/1 3204476]“

(C) 2009 American Institute of Physics. [DOI: 10.1063/1.3204476]“
“Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1.5 % to 2 %. Patients afflicted with severe psoriasis

vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, surveys have shown that patients still do not received optimal treatments.

To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. They were first published in 2006 and updated in 2011. The Guidelines focus on induction therapy in cases of mild, moderate and severe plaque-type psoriasis in adults including systemic P5091 Ubiquitin inhibitor Rigosertib chemical structure therapy, UV therapy and topical therapies.

The therapeutic recommendations were developed based on the results of a systematic literature search and were finalized during

a consensus meeting using structured consensus methods (nominal group process).”
“Hepatitis C virus genotype 6 currently contains 21 recognized subtypes, 6a-6u, for which 6r and 6s lack complete genome sequences. In this study, we entirely sequenced variants QC245 and QC66 from Cambodian immigrants in Canada representing subtypes 6r and 6s, respectively. The two genomes shared 75.3% nucleotide SBC-115076 cell line similarities to each other and 72.0-82.9% to 21 reference sequences representing subtypes 6a 6q, 6t 6u and variants km41 and gz52557. QC66 and QC245 displayed genome lengths of 9473 and 9450 nt and each contained a single open reading frame of 9051 nt. In 10 protein encoding regions QC245 and QC66 shared common sizes with TV249/6t and 537796/6l isolates, respectively. Phylogenetic analyses demonstrated that QC245 was more closely related to subtype 6f, but both QC66 and QC245 were subtypically different from all

other genotype 6 subtypes. Our full-length sequence data confirmed the status of subtype 6r and 6s within genotype 6. Analysis of partial sequences revealed seven 6t and two 6s isolates that were all isolated from Cambodian immigrants. Analysis of the hypervariable region 1 sequences of 81 genotype 6 variants revealed two unique patterns of variation. First, most variants showed an amino acid deletion at the 4th position and second, many contained a basic residue at the 7th position. Possible roles of these two variation patterns are further discussed.”
“Flexural wave in a double-walled carbon nanotube is studied. The scale effect of the carbon nanotube on the wave dispersion is investigated through the nonlocal elastic beam theories.

MMP-2, MT1-MMP, TIMP-2, and TIMP-3 expression were quantitatively

MMP-2, MT1-MMP, TIMP-2, and TIMP-3 expression were quantitatively analysed by immunohistochemistry.

Results: There was significantly higher expression of TIMP-2 (immunopositive area 4.34% versus 0.26%), linked with connective tissue accumulation in the tunica media of varicose veins as compared AZD5582 with arm and neck vein controls. TIMP-2 and TIMP-3 expression was higher in hypertrophic than atrophic segments (3.2% versus 0.99% for TIMP-2, 1.7% versus 0.08% for TIMP-3). Similarly, TIMP-2 and TIMP-3 had elevated expression in the thicker proximal varicose vein segments compared to distal (4.3% versus 1.3% for TIMP-2 and 0.94% versus

0.41% for TIMP-3).

Conclusions: This study linked morphological changes in varicose vein walls with MMP/TIMP balance. A higher TIMP expression favours deposition of connective tissue and thus thicker vein wall, reducing matrix turnover by mTOR inhibitor suppression of protease activity. (C) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.”
“The behavior of 10,10-dimethyl-9-trimethylsiloxy-9,10-dihydrophenanthrene-9-carbonitrile in trifluoromethanesulfonic acid and acid systems CF(3)SO(3)H-CD(2)Cl(2), HSO(3)F-SO(2)ClF-CD(2)Cl(3), and CF(3)COOH-CD(2)Cl(2) were studied by NMR

spectroscopy. Principal reaction schemes were determined; the first step in these schemes is protonation of the initial compound at the oxygen or nitrogen atom.”
“OBJECTIVE: Prevention is the best treatment for cerebrovascular disease, which is why early

diagnosis and the immediate treatment of carotid stenosis contribute significantly to reducing the incidence of stroke. Given its silent nature, 80% of stroke cases occur in asymptomatic individuals, emphasizing the importance of screening individuals with carotid stenosis and identifying high-risk groups for the disease. The aim of this study was to determine the prevalence and the most frequent risk factors for carotid stenosis.

METHODS: A transversal study was conducted in the form of a stroke prevention campaign Savolitinib datasheet held on three nonconsecutive Saturdays. During the sessions, carotid stenosis diagnostic procedures were performed for 500 individuals aged 60 years or older who had systemic arterial hypertension and/or diabetes mellitus and/or coronary heart disease and/or a family history of stroke.

RESULTS: The prevalence of carotid stenosis in the population studied was 7.4%, and the most frequent risk factors identified were mean age of 70 years, carotid bruit, peripheral obstructive arterial disease, coronary insufficiency and smoking. Independent predictive factors of carotid stenosis include the presence of carotid bruit or peripheral obstructive heart disease and/or coronary insufficiency.

CONCLUSIONS: The population with peripheral obstructive heart disease and carotid bruit should undergo routine screening for carotid stenosis.

For such heterogeneous populations, the t-test and ANCOVA method

For such heterogeneous populations, the t-test and ANCOVA method often fail to provide the desired treatment efficacy. We propose an alternative approach for the efficacy evaluation of dietary supplements and functional foods based on a change-point linear regression model. The model does not require the assumption of a constant treatment effect and provides clinically interpretable results. By employing the AIC-based profile likelihood method, inferences can be made easily using CX-4945 standard statistical software. The proposed

method was applied to the Garcinia study data, and the merit of the method was demonstrated by comparing it with traditional methods.”
“Objective: The angiotensinogen (AGT) gene has been shown to be involved in the development of coronary heart disease (CHD). However, the results have been inconsistent. In this study, the authors performed a meta-analysis to clarify the associations between AGT polymorphisms and CHD risk among the Chinese population.

Methods: Published literature from PubMed, the China National Knowledge Infrastructure and Wanfang Data were searched. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a fixed- or random-effects Apoptosis Compound Library nmr model.

Results: Fourteen studies (2540 cases and 2173 controls) for M235T polymorphism and

five studies (655 cases and 815 controls) for T174M polymorphism were included in the meta-analyses. The results Pictilisib cost showed that M235T polymorphism was significantly associated with CHD risk under a recessive model (OR=1.65, 95% CI 1.22-2.25). There

was also significant association between T174M polymorphism and CHD risk under a homogeneous co-dominant model (OR= 4.20, 95% CI 1.90-9.29) and a recessive model (OR=4.15, 95% CI 1.88-9.15). Further sensitivity analyses confirmed the significant association.

Conclusions: The meta-analyses indicated the significant associations of two AGT polymorphisms (M235T, T174M) with CHD risk in the Chinese population.”
“About 25,000 rice T-DNA insertional mutant lines were generated using the vector pCAS04 which has both promoter-trapping and activation-tagging function. Southern blot analysis revealed that about 40% of these Mutants were single copy integration and the average T-DNA insertion number was 2.28. By extensive phenotyping in the field, quite a number of agronomically important mutants were obtained. Histochemical GUS assay with 4,3 10 primary mutants revealed that the GUS-staining frequency was higher than that of the previous reports in various tissues and especially high in flowers. The T-DNA flanking sequences of some mutants were isolated and the T-DNA insertion sites were mapped to the rice genome. The flanking sequence analysis demonstrated the different integration pattern of the right border and left border into rice genome. Compared with Arabidopsis and poplar, it is much varied in the T-DNA border junctions in rice.

The minimum detectable concentrations of mouse IgG for 77 and 155

The minimum detectable concentrations of mouse IgG for 77 and 155 MHz Love wave SAW biosensors and a surface plasmon resonance (SPR) biosensor selleck chemical were found to be 2.5, 1, and 1 mu g/mL, respectively. The fabricated Love wave SAW and SPR biosensors showed similar performances in detectable concentrations of mouse IgG and in coefficient of determination.”
“Although pulmonary toxicity from sirolimus is well recognized, the biochemically homologous everolimus has until recently been thought to be free from this side effect. Emerging evidence suggests an association between

high-dose everolimus and symptomatic pneumonitis. Toxicity at typical immunosuppressive doses has also been described. In support of these observations, we report the occurrence of clinical pneumonitis in 3 patients in association check details with everolimus therapy after heart transplantation in the absence of other causative factors. Typical onset consisted of dyspnea, hypoxemia, and bilateral diffuse pulmonary infiltrates beginning between 2 weeks and 6 months after commencement of the drug. Although uncommon, everolimus may cause pneumonitis and should be considered

in the differential diagnosis of pulmonary infiltrates and hypoxemia in an appropriate clinical setting. J Heart Lung Transplant 2009;28:104-6. Crown Copyright (C) 2009 Published by Elsevier Inc. on behalf of the International Society for Heart and Lung Transplantation. All rights reserved.”
“Background: The aim of this retrospective study was to explore the relationship between psychotropic medication dosage and birth outcomes.

Methods: A total of 136 women were enrolled, who had an active mental disorder, were taking medication to prevent a relapse, or had

a history of postpartum depression or psychosis. Medication use was evaluated for the three trimesters and during labor. Based on the defined daily dose, medication use was classified into three groups. Primary outcome variables included the infant gestational age at birth, birth weight, and Apgar scores at one and 5 minutes.

Results: Our study showed a significantly higher incidence of Apgar MS-275 supplier score <= 7 at 5 minutes in women taking psychotropic drugs as compared with the group taking no medication, respectively (16.3% versus 0.0%, P=0.01). There was no significant difference between the two groups in Apgar score at one minute or in gestational age and birth weight. The results showed no significant differences in gestational age, birth weight, or Apgar scores for a low-intermediate or high dose of a selective serotonin reuptake inhibitor and for a low or intermediate dose of an antipsychotic.

Conclusion: This study does not indicate a relationship between doses of selective serotonin reuptake inhibitors and antipsychotics and adverse neonatal outcomes.

Treatment with anti-tuberculin drugs resulted in resolution of sy

Treatment with anti-tuberculin drugs resulted in resolution of symptoms with a reduction in Ca-125 to normal.

Laparoscopic biopsy with frozen section evaluation would spare patients with peritoneal tuberculosis from unnecessary extensive surgery. Serum Ca-125 level may be useful in monitoring treatment response.”
“Aim: Osteoporosis is a common long-term complication of type 1 diabetes (T1DM). We aimed to determine whether bone mineral density (BMD) and turnover are already

altered during childhood.

Patients and Methods: We recruited 27 T1DM children and 32 controls (age 10.5 +/- BYL719 molecular weight 2.5 yr.) and measured BMD (dual-energy x-ray absorptiometry); bone biomarkers levels (osteocalcin: OC; procollagen type 1 propeptides amino-terminal: PINP; crosslinking telopeptides of type 1 collagen C-terminal: CTX), glycated hemoglobin (HbA1c), dietary intake and physical activity.

Results: Patients with T1DM had lower levels of OC (70.3 +/- 3.3 vs 105.3 +/- 6.8), PINP (556.4 selleck compound +/- 47.6 vs 716.3 +/- 53.8), CTX(0.97 +/- 0.07 vs 1.20 +/- 0.08), physical activity, and calcium intake. Biomarkers were negatively correlated with HbA1c. Though, BMD was similar among groups and not related to HbA1c, disease duration, physical activity or dietary intakes.

Conclusions: Bone turnover

is altered in T1DM children, whereas BMD remains normal during growth. Physical activity and optimal calcium intakes may improve bone metabolism and delay osteoporosis.”
“Background: The aim of this study was to determine factors associated with self-reported ongoing use of opioid medication one to two months after operative treatment

of musculoskeletal Q-VD-Oph trauma.

Methods: Operatively treated patients (n = 145) with musculoskeletal trauma were evaluated one to two months after surgery. Patients indicated if they were taking opioid pain medication and completed several psychological questionnaires: the Center for Epidemiologic Studies Depression Scale, the Pain Catastrophizing Scale, the Pain Anxiety Symptoms Scale, and the Posttraumatic Stress Disorder Checklist, civilian version. The Numeric Rating Scale was used to measure pain intensity. Disability was measured with use of the Short Musculoskeletal Function Assessment Questionnaire and injury severity was measured with use of the Abbreviated Injury Scale.

Results: Patients who scored higher on the catastrophic thinking, anxiety, posttraumatic stress disorder, and depression questionnaires were significantly more likely (p < 0.001) to report taking opioid pain medications one to two months after surgery, regardless of injury severity, fracture site, or treating surgeon. The magnitude of disability as measured by the Short Musculoskeletal Function Assessment score was significantly higher (p < 0.001) in the patients who reported using opioids (40 points) compared with those who reported not using opioids (24 points).

Size and number of metastases as well as re-do metastasectomy wer

Size and number of metastases as well as re-do metastasectomy were not associated with worse survival. (C) 2012 Elsevier Ltd. All rights reserved.”
“The inclusion complexes between a series of cyclodextrins (CDs), which are alpha CD, beta CD, delta CD and hydroxypropyl-beta-CD (HP beta CD), and eugenol was studied by spectroscopy, thermal analysis and in silico molecular modeling. Molecular modeling provided PF-00299804 datasheet conformation and thermodynamic data, and also confirmed experimental observations that, in aqueous

phase, the complex formation was found at 1:1 mole ratio of eugenol and all CDs except those of gamma CD. Free energy of solvation of CDs and its cavity size are the most crucial factors for complex formation. The aromatic portion of eugenol was partially NVP-BSK805 order incorporated in aCD hydrophobic cavity whereas for beta CD and HP beta CD their aromatic parts could completely translocate

inside. Moreover, a presence of free eugenol absorbed on CD hydrophilic surface were found as the following order, beta CD < HP beta CD < alpha CD, resulting in varying extents of eugenol release profiles. The intermolecular forces were found primarily due to intermolecular hydrogen bonding, resulting in stable complexes. (C) 2009 Elsevier Ltd. All rights reserved.”
“This study aimed to document intraoperative and postoperative complications associated with the use of transvaginal polypropylene mesh in the repair of pelvic organ prolapse (POP).

This is a retrospective review of 127 cases of transvaginal repair of POP using synthetic mesh.

Mean SB431542 manufacturer postoperative value (+/- SD) for pelvic organ prolapse quantification (POPQ) measurements Aa, Ap, and C were: -2.4 +/- 1.1 (cm), -2.4 +/- 0.9 (cm), and -7.7 +/- 1.2 (cm), respectively. The difference between preoperative and postoperative values of these points was significant (p < 0.0001). Mesh erosion rate was 13/127 (10.2%) with significant correlation between mesh erosion and concurrent vaginal hysterectomy (p = 0.008). Combined anterior and posterior vaginal mesh surgery increased the risk of intraoperative bleeding

and blood transfusion (p < 0.05).

Concurrent vaginal hysterectomy is associated with increased risk of vaginal mesh erosion. Combined anterior and posterior vaginal mesh repair is an increased risk factor for intraoperative bleeding and blood transfusion.”
“Radiotherapy is widely used in the treatment of patients with breast cancer, but ionizing radiation-induced carcinogenesis has been described in several studies. Matrix metalloproteinases (MMPs) are a wide family of proteases secreted by tumour and microenvironmental cells that are directly linked with invasion and metastasis through complete extracellular matrix (ECM) breakage. In the past decade, MMPs have been associated with other carcinogenesis steps, including tumour growth and angiogenesis promotion.

However, the structures and functions of these proteins remain un

However, the structures and functions of these proteins remain unknown so far. To gain insight into the function of this family of proteins, we have determined selleck the structure of Atu4866 as a target of a structural

genomics project using solution NMR spectroscopy. Our results reveal that Atu4866 adopts a streptavidin-like fold featuring a beta-barrel/sandwich formed by eight antiparallel beta-strands. Further structural analysis identified a continuous patch of conserved residues on the surface of Atu4866 that may constitute a potential ligand-binding site.”
“Intrinsically-photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and function as irradiance detectors, responsible for crucial non-image forming visual functions. In addition to their intrinsic photosensitivity, ipRGCs are also activated by synaptic inputs originating at the classical photoreceptors, rods and cones. Little is known about inhibition through these retinal pathways, despite ipRGCs receiving massive synaptic inputs from inhibitory amacrine interneurons. We performed a wide anatomical screening for neurotransmitter receptors possibly involved in the inhibitory modulation

of ipRGCs in the macaque retina. We investigated Forskolin in vivo both subtypes of primate ipRGCs described so far and report that outer-stratifying (M1) cells possess mainly GlyR alpha 2 and GABA(A)R alpha 3 subunits, while inner-stratifying (M2) cells are overall subject to less inhibitory modulation. Our results suggest that M1 and M2 ipRGC subtypes are modulated via distinct inhibitory intraretinal circuits. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The bacterial leucine-responsive regulatory protein (Lrp) is a global transcriptional regulator that controls the expression of many genes during starvation and the transition Oxygenase to stationary phase. The Mycobacterium tuberculosis gene Rv3291c encodes a 150-amino acid protein (designated here as Mtb LrpA) with homology with Escherichia coli Lrp. The crystal structure of the native form of Mtb

LrpA was solved at 2.1 angstrom. The Mtb LrpA structure shows an N-terminal DNA-binding domain with a helix-turn-helix (HTH) motif, and a C-terminal regulatory domain. In comparison to the complex of E. coli AsnC with asparagine, the effector- binding pocket (including loop 100-106) in LrpA appears to be largely preserved, with hydrophobic substitutions consistent with its specificity for leucine. The effector-binding pocket is formed at the interface between adjacent dimers, with an opening to the core of the octamer as in AsnC, and an additional substrate-access channel opening to the outer surface of the octamer. Using electrophoretic mobility shift assays, purified Mtb LrpA protein was shown to form a protein-DNA complex with the lat promoter, demonstrating that the lat operon is a direct target of LrpA.