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Year of Publication
1.  Dynamic Oscillatory Signatures of Central Neuropathic Pain in Spinal Cord Injury 
The Journal of Pain  2014;15(6):645-655.
Central neuropathic pain (CNP) is believed to be accompanied by increased activation of the sensorimotor cortex. Our knowledge of this interaction is based mainly on functional magnetic resonance imaging studies, but there is little direct evidence on how these changes manifest in terms of dynamic neuronal activity. This study reports on the presence of transient electroencephalography (EEG)-based measures of brain activity during motor imagery in spinal cord–injured patients with CNP. We analyzed dynamic EEG responses during imaginary movements of arms and legs in 3 groups of 10 volunteers each, comprising able-bodied people, paraplegic patients with CNP (lower abdomen and legs), and paraplegic patients without CNP. Paraplegic patients with CNP had increased event-related desynchronization in the theta, alpha, and beta bands (16–24 Hz) during imagination of movement of both nonpainful (arms) and painful limbs (legs). Compared to patients with CNP, paraplegics with no pain showed a much reduced power in relaxed state and reduced event-related desynchronization during imagination of movement. Understanding these complex dynamic, frequency-specific activations in CNP in the absence of nociceptive stimuli could inform the design of interventional therapies for patients with CNP and possibly further understanding of the mechanisms involved.
Perspective
This study compares the EEG activity of spinal cord–injured patients with CNP to that of spinal cord–injured patients with no pain and also to that of able-bodied people. The study shows that the presence of CNP itself leads to frequency-specific EEG signatures that could be used to monitor CNP and inform neuromodulatory treatments of this type of pain.
doi:10.1016/j.jpain.2014.02.005
PMCID: PMC4058526  PMID: 24589821
Central neuropathic pain; spinal cord injury; event-related synchronization/desynchronization; motor imagery; electroencephalography
2.  InterProScan 5: genome-scale protein function classification 
Bioinformatics  2014;30(9):1236-1240.
Motivation: Robust large-scale sequence analysis is a major challenge in modern genomic science, where biologists are frequently trying to characterize many millions of sequences. Here, we describe a new Java-based architecture for the widely used protein function prediction software package InterProScan. Developments include improvements and additions to the outputs of the software and the complete reimplementation of the software framework, resulting in a flexible and stable system that is able to use both multiprocessor machines and/or conventional clusters to achieve scalable distributed data analysis. InterProScan is freely available for download from the EMBl-EBI FTP site and the open source code is hosted at Google Code.
Availability and implementation: InterProScan is distributed via FTP at ftp://ftp.ebi.ac.uk/pub/software/unix/iprscan/5/ and the source code is available from http://code.google.com/p/interproscan/.
Contact: http://www.ebi.ac.uk/support or interhelp@ebi.ac.uk or mitchell@ebi.ac.uk
doi:10.1093/bioinformatics/btu031
PMCID: PMC3998142  PMID: 24451626
3.  EBI metagenomics—a new resource for the analysis and archiving of metagenomic data 
Nucleic Acids Research  2013;42(D1):D600-D606.
Metagenomics is a relatively recently established but rapidly expanding field that uses high-throughput next-generation sequencing technologies to characterize the microbial communities inhabiting different ecosystems (including oceans, lakes, soil, tundra, plants and body sites). Metagenomics brings with it a number of challenges, including the management, analysis, storage and sharing of data. In response to these challenges, we have developed a new metagenomics resource (http://www.ebi.ac.uk/metagenomics/) that allows users to easily submit raw nucleotide reads for functional and taxonomic analysis by a state-of-the-art pipeline, and have them automatically stored (together with descriptive, standards-compliant metadata) in the European Nucleotide Archive.
doi:10.1093/nar/gkt961
PMCID: PMC3965009  PMID: 24165880
5.  Temporal modulation transfer functions in cochlear implantees using a method that limits overall loudness cues 
Hearing Research  2012;283(1-2):59-69.
Temporal modulation transfer functions (TMTFs) were measured for six users of cochlear implants, using different carrier rates and levels. Unlike most previous studies investigating modulation detection, the experimental design limited potential effects of overall loudness cues. Psychometric functions (percent correct discrimination of modulated from unmodulated stimuli versus modulation depth) were obtained. For each modulation depth, each modulated stimulus was loudness balanced to the unmodulated reference stimulus, and level jitter was applied in the discrimination task. The loudness-balance data showed that the modulated stimuli were louder than the unmodulated reference stimuli with the same average current, thus confirming the need to limit loudness cues when measuring modulation detection. TMTFs measured in this way had a low-pass characteristic, with a cut-off frequency (at comfortably loud levels) similar to that for normal-hearing listeners. A reduction in level caused degradation in modulation detection efficiency and a lower-cut-off frequency (i.e. poorer temporal resolution). An increase in carrier rate also led to a degradation in modulation detection efficiency, but only at lower levels or higher modulation frequencies. When detection thresholds were expressed as a proportion of dynamic range, there was no effect of carrier rate for the lowest modulation frequency (50 Hz) at either level.
Highlights
► Loudness cues lead to overestimation of modulation detection ability in cochlear implantees. ► Implantees show similar temporal resolution ability to normal-hearing listeners. ► Modulation sensitivity is poorer at higher carrier rates for some conditions. ► Modulation sensitivity is poorer at lower levels.
doi:10.1016/j.heares.2011.11.009
PMCID: PMC3314947  PMID: 22146425
CI, cochlear implant; CL, current level; DL, difference limen; DR, dynamic range; m, modulation index; MCL, maximum comfortable level; MDT, modulation detection threshold; MP, monopolar; NIFC, n-interval forced choice; TMTF, temporal modulation transfer function
6.  InterPro in 2011: new developments in the family and domain prediction database 
Nucleic Acids Research  2011;40(D1):D306-D312.
InterPro (http://www.ebi.ac.uk/interpro/) is a database that integrates diverse information about protein families, domains and functional sites, and makes it freely available to the public via Web-based interfaces and services. Central to the database are diagnostic models, known as signatures, against which protein sequences can be searched to determine their potential function. InterPro has utility in the large-scale analysis of whole genomes and meta-genomes, as well as in characterizing individual protein sequences. Herein we give an overview of new developments in the database and its associated software since 2009, including updates to database content, curation processes and Web and programmatic interfaces.
doi:10.1093/nar/gkr948
PMCID: PMC3245097  PMID: 22096229
7.  Cross-Talk and Sensitization of Bladder Afferent Nerves 
Neurourology and urodynamics  2010;29(1):77-81.
Chronic pelvic pain (CPP) disorders are a heterogenous group of overlapping conditions involving the bladder, bowel, and other pelvic visceral structures. CPP is a poorly understood, often debilitating condition affecting both men and women. The development of pelvic organ cross-sensitization, and often ensuing CPP, following acute or chronic pelvic visceral irritation or stimulation is facilitated by anatomic apposition, coordinated physiologic and reflexive pathways (cross-talk), and convergent sensory input of the pelvic viscera, their associated striated sphincters, muscular components of the pelvic floor, pelvic abdominal wall, and perineum and corresponding cutaneous components, which together facilitate daily coordinated conscious pelvic physiologic activity. Correspondingly, the causes of CPP are numerous and may include gynecologic, urologic, gastrointestinal, musculoskeletal, neural, or psychologic origins, as well as combinations thereof. Although efficacious therapeutic options are limited for those afflicted (the US estimate for women alone is 9.2 million [1]), further research and multi-disciplinary approaches will no doubt improve patient quality of life and decrease direct and indirect annual costs to society, which currently is estimated to exceed ≈$3 billion [1]. CPP not only encompasses pain syndromes of the pelvic cavity, such as interstitial cystitis/painful bladder syndrome (IC/PBS) and irritable bowel syndrome (IBS) but also includes those of the pelvic floor, including vulvodynia, orchialgia, urethral syndrome, and chronic prostatitis (male CPP syndrome) [2]. Since the distal colon and urinary bladder are two pelvic organs whose functions are an integral part of daily, conscious, physiologic pelvic activity, it is not surprising that IBS and IC/PBS, analogous disorders of pelvic visceral pain and urgency, are probably the most common CPP disorders in the general population [1–4].
doi:10.1002/nau.20817
PMCID: PMC2805190  PMID: 20025032
8.  Convergence of Bladder and Colon Sensory Innervation Occurs at the Primary Afferent Level 
Pain  2006;128(3):235-243.
Dichotomizing afferents are individual dorsal root ganglion (DRG) neurons that innervate two distinct structures thereby providing a form of afferent convergence that may be involved in pelvic organ cross-sensitization. To determine the distribution of dichotomizing afferents supplying the distal colon and bladder of the Sprague-Dawley rat and the C57Bl/6 mouse, we performed concurrent retrograde labeling of urinary bladder and distal colon afferents using cholera toxin subunit B (CTB) fluorescent conjugates. Animals were perfused 4–5 days after sub-serosal organ injections, and the T10-S2 DRG were removed, sectioned, and analyzed using confocal microscopy. In the rat, CTB-positive afferents retrogradely labeled from the bladder were nearly 3 times more numerous than those labeled from the distal colon, while in the mouse, each organ was equally represented. In both species, the majority of colon and bladder afferents projected from lumbosacral (LS) ganglia and secondarily from thoracolumbar (TL) ganglia. In the rat, 17% of the total CTB-positive neurons were retrogradely labeled from both organs with 11% localized in TL, 6% in LS, and 0.8% in thoracic (TH) ganglia. In the mouse, 21% of the total CTB-positive neurons were dually-labeled with 12% localized in LS, 4% in TH, and 4% in TL ganglia. These findings support the existence of dichotomizing pelvic afferents, which provide a pre-existing neuronal substrate for possible immediate and maintained pelvic organ cross-sensitization and ultimately may play a role in the overlap of pelvic pain disorders.
doi:10.1016/j.pain.2006.09.023
PMCID: PMC1892845  PMID: 17070995
Cholera toxin B; Alexa Fluor; Retrograde Labeling; Convergence; Doral Root Ganglia
9.  Enhanced Expression of Mast Cell Growth Factor and Mast Cell Activation in the Bladder Following the Resolution of Trinitrobenzenesulfonic Acid (TNBS) Colitis in Female Rats 
Neurourology and urodynamics  2007;26(6):887-893.
Aims
Chronic pelvic pain disorders often overlap. We have shown that acute colonic irritation can produce acute irritative micturition patterns and acutely sensitize bladder afferent responses to mechanical and chemical stimuli. We hypothesize that with time, colonic irritation can lead to neurogenic changes in the bladder and the development of chronic bladder sensitization.
Methods
Micturition patterns were measured in rats 60–90 days after the induction of trinitrobenzenesulfonic acid (TNBS) colitis in the resolution phase of this model. Total and activated mast cells (MCs) were quantified in the bladder, while mRNA levels of stem cell factor (SCF) (a.k.a. MC growth factor) and nerve growth factor (NGF) (a MC and nociceptive C-fiber stimulator) were quantified in the bladder and L6-S1 dorsal root ganglia (DRG).
Results
Following intra-rectal TNBS, voiding volume was reduced (p<0.005), while voiding frequency was increased (p<0.05), both by ~50%. Furthermore, both the percentage and density of activated bladder MCs were significantly elevated (p<0.05), although total MC counts were not statistically increased. At the molecular level, urinary bladder SCF expression increased 2-fold (p<0.005), as did NGF (p<0.01), while L6-S1 DRG levels were not significantly elevated.
Conclusions
Chronic cystitis in the rat as evidenced by changes in micturition patterns and the recruitment of activated MCs can occur during the resolution phase of TNBS colitis. These changes, of which MCs may play an important role, appear to be maintained over time and may occur via stimulation of convergent pelvic afferent input resulting in the upregulation of neurotrophic factors in the target organ.
doi:10.1002/nau.20410
PMCID: PMC2092453  PMID: 17385238
Stem cell factor; Bowel; Neurogenic Cystitis; Micturition; Degranulation

Results 1-9 (9)