Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes

A genome-scale flux model for primary metabolism of Neisseria meningitidis was constructed; a minimal medium for growth of N. meningitidis was designed using the model and tested successfully in batch and chemostat cultures

Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters

When, where and how osteoporosis-associated fractures occur: An analysis from the global longitudinal study of osteoporosis in women (GLOW)

Objective: To examine when, where and how fractures occur in postmenopausal women. Methods: We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3. Results: Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68-86% of NHNV and 68-83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling. Conclusion: In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year. © 2013 Costa et al

Developmental Robustness by Obligate Interaction of Class B Floral Homeotic Genes and Proteins

DEF-like and GLO-like class B floral homeotic genes encode closely related MADS-domain transcription factors that act as developmental switches involved in specifying the identity of petals and stamens during flower development. Class B gene function requires transcriptional upregulation by an autoregulatory loop that depends on obligate heterodimerization of DEF-like and GLO-like proteins. Because switch-like behavior of gene expression can be displayed by single genes already, the functional relevance of this complex circuitry has remained enigmatic. On the basis of a stochastic in silico model of class B gene and protein interactions, we suggest that obligate heterodimerization of class B floral homeotic proteins is not simply the result of neutral drift but enhanced the robustness of cell-fate organ identity decisions in the presence of stochastic noise. This finding strongly corroborates the view that the appearance of this regulatory mechanism during angiosperm phylogeny led to a canalization of flower development and evolution

Pretreatment organ function in patients with advanced head and neck cancer: clinical outcome measures and patients' views

<p>Abstract</p> <p>Background</p> <p>Aim of this study is to thoroughly assess pretreatment organ function in advanced head and neck cancer through various clinical outcome measures and patients' views.</p> <p>Methods</p> <p>A comprehensive, multidimensional assessment was used, that included quality of life, swallowing, mouth opening, and weight changes. Fifty-five patients with stage III-IV disease were entered in this study prior to organ preserving (chemoradiation) treatment.</p> <p>Results</p> <p>All patients showed pretreatment abnormalities or problems, identified by one or more of the outcome measures. Most frequent problems concerned swallowing, pain, and weight loss. Interestingly, clinical outcome measures and patients' perception did no always concur. E.g. videofluoroscopy identified aspiration and laryngeal penetration in 18% of the patients, whereas only 7 patients (13%) perceived this as problematic; only 2 out of 7 patients with objective trismus actually perceived trismus.</p> <p>Conclusion</p> <p>The assessment identified several problems already pre-treatment, in this patient population. A thorough assessment of both clinical measures and patients' views appears to be necessary to gain insight in all (perceived) pre-existing functional and quality of life problems.</p

Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise

Corrected by: Erratum: Molecular Psychiatry (2016) 21, 1645–1645; doi:10.1038/mp.2016.57; published online 19 April 2016. Following publication of the above article, the authors noticed that the second author’s name was presented incorrectly. The author’s name should have appeared as M Fiatarone Singh. The publisher regrets the error.Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.±6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (Pcorrected <0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.Molecular Psychiatry advance online publication, 22 March 2016; doi:10.1038/mp.2016.19.C Suo, M Fiatarone Singh, N Gates, W Wen, P Sachdev, H Brodaty, N Saigal, GC Wilson, J Meiklejohn, N Singh, BT Baune, M Baker, N Foroughi, Y Wang, Y Mavros, A Lampit, I Leung, and MJ Valenzuel

Metabolomic analysis of human disease and its application to the eye

Metabolomics, the analysis of the metabolite profile in body fluids or tissues, is being applied to the analysis of a number of different diseases as well as being used in following responses to therapy. While genomics involves the study of gene expression and proteomics the expression of proteins, metabolomics investigates the consequences of the activity of these genes and proteins. There is good reason to think that metabolomics will find particular utility in the investigation of inflammation, given the multi-layered responses to infection and damage that are seen. This may be particularly relevant to eye disease, which may have tissue specific and systemic components. Metabolomic analysis can inform us about ocular or other body fluids and can therefore provide new information on pathways and processes involved in these responses. In this review, we explore the metabolic consequences of disease, in particular ocular conditions, and why the data may be usefully and uniquely assessed using the multiplexed analysis inherent in the metabolomic approach

Use of 1H and 31P HRMAS to evaluate the relationship between quantitative alterations in metabolite concentrations and tissue features in human brain tumour biopsies

[EN] Quantitative multinuclear high-resolution magic angle spinning (HRMAS) was performed in order to determine the tissue pH values of and the absolute metabolite concentrations in 33 samples of human brain tumour tissue. Metabolite concentrations were quantified by 1D 1 H and 31P HRMAS using the electronic reference to in vivo concentrations (ERETIC) synthetic signal. 1 H–1 H homonuclear and 1 H–31P heteronuclear correlation experiments enabled the direct assessment of the 1 H–31P spin systems for signals that suffered from overlapping in the 1D 1 H spectra, and linked the information present in the 1D 1 H and 31P spectra. Afterwards, the main histological features were determined, and high heterogeneity in the tumour content, necrotic content and nonaffected tissue content was observed. The metabolite profiles obtained by HRMAS showed characteristics typical of tumour tissues: rather low levels of energetic molecules and increased concentrations of protective metabolites. Nevertheless, these characteristics were more strongly correlated with the total amount of living tissue than with the tumour cell contents of the samples alone, which could indicate that the sampling conditions make a significant contribution aside from the effect of tumour development in vivo. The use of methylene diphosphonic acid as a chemical shift and concentration reference for the 31P HRMAS spectra of tissues presented important drawbacks due to its interaction with the tissue. Moreover, the pH data obtained from 31P HRMAS enabled us to establish a correlation between the pH and the distance between the N(CH3)3 signals of phosphocholine and choline in 1 H spectra of the tissue in these tumour samples.The authors acknowledge the SCSIE-University of Valencia Microscopy Service for the histological preparations. They also acknowledge Martial Piotto (Bruker BioSpin, France) for providing the ERETIC synthetic signal. Furthermore, they acknowledge financial support from the Spanish Government project SAF2007-6547, the Generalitat Valenciana project GVACOMP2009-303, and the E.U.'s VI Framework Programme via the project "Web accessible MR decision support system for brain tumor diagnosis and prognosis, incorporating in vivo and ex vivo genomic and metabolomic data" (FP6-2002-LSH 503094). CIBER-BBN is an initiative funded by the VI National R&D&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Esteve Moya, V.; Celda, B.; Martínez Bisbal, MC. (2012). Use of 1H and 31P HRMAS to evaluate the relationship between quantitative alterations in metabolite concentrations and tissue features in human brain tumour biopsies. Analytical and Bioanalytical Chemistry. 403:2611-2625. https://doi.org/10.1007/s00216-012-6001-zS26112625403Cheng LL, Chang IW, Louis DN, Gonzalez RG (1998) Cancer Res 58:1825–1832Opstad KS, Bell BA, Griffiths JR, Howe FA (2008) Magn Reson Med 60:1237–1242Sjobakk TE, Johansen R, Bathen TF, Sonnewald U, Juul R, Torp SH, Lundgren S, Gribbestad IS (2008) NMR Biomed 21:175–185Martinez-Bisbal MC, Marti-Bonmati L, Piquer J, Revert A, Ferrer P, Llacer JL, Piotto M, Assemat O, Celda B (2004) NMR Biomed 17:191–205Erb G, Elbayed K, Piotto M, Raya J, Neuville A, Mohr M, Maitrot D, Kehrli P, Namer IJ (2008) Magn Reson Med 59:959–965Wilson M, Davies NP, Brundler MA, McConville C, Grundy RG, Peet AC (2009) Mol Cancer 8:6Martinez-Bisbal MC, Monleon D, Assemat O, Piotto M, Piquer J, Llacer JL, Celda B (2009) NMR Biomed 22:199–206Martínez-Granados B, Monleón D, Martínez-Bisbal MC, Rodrigo JM, del Olmo J, Lluch P, Ferrández A, Martí-Bonmatí L, Celda B (2006) NMR Biomed 19:90–100Hubesch B, Sappey-Marinier D, Roth K, Meyerhoff DJ, Matson GB, Weiner MW (1990) Radiology 174:401–409Albers MJ, Krieger MD, Gonzalez-Gomez I, Gilles FH, McComb JG, Nelson MD Jr, Bluml S (2005) Magn Reson Med 53:22–29Wijnen JP, Scheenen TW, Klomp DW, Heerschap A (2010) NMR Biomed 23:968–976Podo F (1999) NMR Biomed 12:413–439Griffiths JR, Cady E, Edwards RH, McCready VR, Wilkie DR, Wiltshaw E (1983) Lancet 1:1435–1436Robitaille PL, Robitaille PA, Gordon Brown G, Brown GG (1991) J Magn Reson 92:73–84, 1969Griffiths JR (1991) Br J Cancer 64:425–427Payne GS, Troy H, Vaidya SJ, Griffiths JR, Leach MO, Chung YL (2006) NMR Biomed 19:593–598De Silva SS, Payne GS, Thomas V, Carter PG, Ind TE, deSouza NM (2009) NMR Biomed 22:191–198Wang Y, Cloarec O, Tang H, Lindon JC, Holmes E, Kochhar S, Nicholson JK (2008) Anal Chem 80:1058–1066Lehnhardt FG, Rohn G, Ernestus RI, Grune M, Hoehn M (2001) NMR Biomed 14:307–317Srivastava NK, Pradhan S, Gowda GA, Kumar R (2010) NMR Biomed 23:113–122Akoka S, Barantin L, Trierweiler M (1999) Anal Chem 71:2554–2557Albers MJ, Butler TN, Rahwa I, Bao N, Keshari KR, Swanson MG, Kurhanewicz J (2009) Magn Reson Med 61:525–532Ben Sellem D, Elbayed K, Neuville A, Moussallieh FM, Lang-Averous G, Piotto M, Bellocq JP, Namer IJ (2011) J Oncol 2011:174019Bourne R, Dzendrowskyj T, Mountford C (2003) NMR Biomed 16:96–101Martinez-Bisbal MC, Esteve V, Martinez-Granados B, Celda B (2011) J Biomed Biotechnol 2011:763684, Epub 2010 Sep 5Celda B, Montelione GT (1993) J Magn Reson B 101:189–193Esteve V, Celda B (2008) Magn Reson Mater Phys MAGMA 21:484–484Collins TJ (2007) Biotechniques 43:25–30Govindaraju V, Young K, Maudsley AA (2000) NMR Biomed 13:129–153Fan TW-M (1996) Prog Nucl Magn Reson Spectrosc 28:161–219Ulrich EL, Akutsu H, Doreleijers JF, Harano Y, Ioannidis YE, Lin J, Livny M, Mading S, Maziuk D, Miller Z, Nakatani E, Schulte CF, Tolmie DE, Kent Wenger R, Yao H, Markley JL (2008) Nucleic Acids Res 36:D402–D408Kriat M, Vion-Dury J, Confort-Gouny S, Favre R, Viout P, Sciaky M, Sari H, Cozzone PJ (1993) J Lipid Res 34:1009–1019Subramanian A, Shankar Joshi B, Roy AD, Roy R, Gupta V, Dang RS (2008) NMR Biomed 21:272–288Daykin CA, Corcoran O, Hansen SH, Bjornsdottir I, Cornett C, Connor SC, Lindon JC, Nicholson JK (2001) Anal Chem 73:1084–1090Griffin JL, Lehtimaki KK, Valonen PK, Grohn OH, Kettunen MI, Yla-Herttuala S, Pitkanen A, Nicholson JK, Kauppinen RA (2003) Cancer Res 63:3195–3201Petroff OAC, Prichard JW (1995) In: Kraicer J, Dixon SJ (eds) Methods in neurosciences. Academic, San DiegoBarton S, Howe F, Tomlins A, Cudlip S, Nicholson J, Anthony Bell B, Griffiths J (1999) Magn Reson Mater Phys Biol Med 8:121–128Sitter B, Sonnewald U, Spraul M, Fjosne HE, Gribbestad IS (2002) NMR Biomed 15:327–337Coen M, Hong YS, Cloarec O, Rhode CM, Reily MD, Robertson DG, Holmes E, Lindon JC, Nicholson JK (2007) Anal Chem 79:8956–8966Russell D, Rubinstein LJ (1998) Russel and Rubinstein's pathology of tumors of the nervous system. Arnold, LondonTynkkynen T, Tiainen M, Soininen P, Laatikainen R (2009) Anal Chim Acta 648:105–112Kjaergaard M, Brander S, Poulsen F (2011) J Biomol NMR 49:139–149Robert O, Sabatier J, Desoubzdanne D, Lalande J, Balayssac S, Gilard V, Martino R, Malet-Martino M (2011) Anal Bioanal Chem 399:987–999Chadzynski GL, Bender B, Groeger A, Erb M, Klose U (2011) J Magn Reson 212:55–63Weljie AM, Jirik FR (2011) Int J Biochem Cell Biol 43:981–989Barba I, Cabanas ME, Arus C (1999) Cancer Res 59:1861–1868Liimatainen T, Hakumaki JM, Kauppinen RA, Ala-Korpela M (2009) NMR Biomed 22:272–279Opstad KS, Bell BA, Griffiths JR, Howe FA (2008) NMR Biomed 21:677–685Schmitz JE, Kettunen MI, Hu D, Brindle KM (2005) Magn Reson Med 54:43–50Glunde K, Artemov D, Penet MF, Jacobs MA, Bhujwalla ZM (2010) Chem Rev 110:3043–3059Hertz L (2008) Neuropharmacology 55:289–309Takahashi T, Otsuguro K, Ohta T, Ito S (2010) Br J Pharmacol 161:1806–181

Surgery for scapula process fractures: Good outcome in 26 patients

Background Generally, scapula process fractures (coracoid and acromion) have been treated nonoperatively with favorable outcome, with the exception of widely displaced fractures. Very little has been published, however, regarding the operative management of such fractures and the literature that is available involves very few patients. Our hypothesis was that operative treatment of displaced acromion and coracoid fractures is a safe and effective treatment that yields favorable surgical results