Restless legs syndrome (RLS) is known to be associated with depression. We hypothesized that RLS in depression is linked to the severity, duration, and frequency of depressive episodes.
Materials and Methods:
Subjects fulfilling DSM-IV-TR criteria of depressive disorders were included in this study after seeking informed consent. Using structured interview of MINI-Plus their demographic data and history were recorded. Severity of depression was assessed with the help of HAM-D. Insomnia was diagnosed following ICSD-2 criteria. RLS was diagnosed according to IRLSSG criteria. Descriptive statistics, Chi-square test, independent sample t test and MANOVA were computed with the help of SPSS v 17.0.
RLS was reported by 31.48% of sample. There was no gender difference in prevalence of RLS (X2 =0.46; P=0.33). There was no difference in the age , total duration of depressive illness and number of depressive episodes between RLS and non-RLS groups (F=0.44; P=0.77; Wilk's Lambda=0.96). The HAM-D score was higher in the non-RLS group (P=0.03). Onset of RLS symptoms was not related to onset of depressive symptoms.
RLS is prevalent in depressive disorder. However, onset of RLS is unrelated to age and number or duration of depressive disorders.
Adults; depression; prevalance; restless leg syndrome
Restless legs syndrome (RLS) rarely affects the upper limb during the initial course of disease. We present a patient who complained of symptoms suggesting RLS in the right upper limb as the sole manifestation of illness. Bilateral cervical ribs and depression were co-incidental findings. Patient responded well to dopaminergic therapy.
Cervical ribs; depression; restless leg syndrome
mRNA-Seq is a precise and highly reproducible technique for measurement of transcripts levels and yields sequence information of a transcriptome at a single nucleotide base-level thus enabling us to determine splice junctions and alternative splicing events with high confidence. Often analysis of mRNA-Seq data does not attempt to quantify the expressions at isoform level. In this paper our objective would be use the mRNA-Seq data to infer expression at isoform level, where splicing patterns of a gene is assumed to be known. A Bayesian latent variable based modeling framework is proposed here, where the parameterization enables us to infer at various levels. For example, expression variability of an isoform across different conditions; the model parameterization also allows us to carry out two-sample comparisons, e.g., using a Bayesian t-test, in addition simple presence or absence of an isoform can also be estimated by the use of the latent variables present in the model. In this paper we would carry out inference on isoform expression under different normalization techniques, since it has been recently shown that one of the most prominent sources of variation in differential call using mRNA-Seq data is the normalization method used. The statistical framework is developed for multiple isoforms and easily extends to reads mapping to multiple genes. This could be achieved by slight conceptual modifications in definitions of what we consider as a gene and what as an exon. Additionally proposed framework can be extended by appropriate modeling of the design matrix to infer about yet unknown novel transcripts. However such attempts should be made judiciously since the input date used in the proposed model does not use reads from splice junctions.
mRNA-Seq; isoform expression; Bayesian latent variable modeling; multi-sample comparison; Bayesian t-test; spike-n-slab method
Supratentorial primitive neuroectodermal tumors predominantly occur in children, and are rare in the adult population. Less than 100 cases of supratentorial primitive neuroectodermal tumor have been reported in adults internationally. Our case study reports this rare incident.
A 22-year-old Hispanic man presented with headaches, blurry vision, diplopia, intermittent vomiting, and grossly decreased vision. A magnetic resonance image showed a left posterior parietal heterogeneously enhancing mass measuring 4.2cm × 7.2cm × 7.0cm. After craniotomy for resection and decompression, the mass was histologically revealed to be a supratentorial primitive neuroectodermal tumor. Standardized immunohistochemical studies for this mass were carried out.
We have concluded that immunohistochemical and genetic workup should be included in the standardized pathological workup for primitive neuroectodermal tumors in order to provide more prognostic information. Based on our current literature review, we propose an immunohistochemical panel.
With over 1.3 billion people, India is estimated to contain three times more genetic diversity than does Europe. Next-generation sequencing technologies have facilitated the understanding of diversity by enabling whole genome sequencing at greater speed and lower cost. While genomes from people of European and Asian descent have been sequenced, only recently has a single male genome from the Indian subcontinent been published at sufficient depth and coverage. In this study we have sequenced and analyzed the genome of a South Asian Indian female (SAIF) from the Indian state of Kerala.
We identified over 3.4 million SNPs in this genome including over 89,873 private variations. Comparison of the SAIF genome with several published personal genomes revealed that this individual shared ~50% of the SNPs with each of these genomes. Analysis of the SAIF mitochondrial genome showed that it was closely related to the U1 haplogroup which has been previously observed in Kerala. We assessed the SAIF genome for SNPs with health and disease consequences and found that the individual was at a higher risk for multiple sclerosis and a few other diseases. In analyzing SNPs that modulate drug response, we found a variation that predicts a favorable response to metformin, a drug used to treat diabetes. SNPs predictive of adverse reaction to warfarin indicated that the SAIF individual is not at risk for bleeding if treated with typical doses of warfarin. In addition, we report the presence of several additional SNPs of medical relevance.
This is the first study to report the complete whole genome sequence of a female from the state of Kerala in India. The availability of this complete genome and variants will further aid studies aimed at understanding genetic diversity, identifying clinically relevant changes and assessing disease burden in the Indian population.
Indian genome; Personal genomics; Whole genome sequencing
Earlier studies conducted among migraineurs have shown an association between migraine and restless legs syndrome (RLS). We chose RLS patients and looked for migraine to exclude sample bias.
Materials and Methods:
99 consecutive subjects of idiopathic RLS were recruited from the sleep clinic during four months period. Physician diagnosis of headache and depressive disorder was made with the help of ICHD-2 and DSM-IV-TR criteria, respectively. Sleep history was gathered. Severity of RLS and insomnia was measured using IRLS (Hindi version) and insomnia severity index Hindi version, respectively. Chi-square test, one way ANOVA and t-test were applied to find out the significance.
Primary headache was seen in 51.5% cases of RLS. Migraine was reported by 44.4% subjects and other types of ‘primary headaches’ were reported by 7.1% subjects. Subjects were divided into- RLS; RLS with migraine and RLS with other headache. Females outnumbered in migraine subgroup (χ2=16.46, P<0.001). Prevalence of depression (χ2=3.12, P=0.21) and family history of RLS (χ2=2.65, P=0.26) were not different among groups. Severity of RLS (P=0.22) or insomnia (P=0.43) were also similar.
Migraine is frequently found in RLS patients in clinic based samples. Females with RLS are prone to develop migraine. Depression and severity of RLS or insomnia do not affect development of headache.
Migraine; primary headache; restless legs syndrome
Rumination syndrome is known to exist in infants and mentally retarded adults since long time. In past few years, some reports appeared that showed its existence in adult patients also. It is frequently confused with the intractable vomiting in adults and misdiagnosis leads to delay in appropriate management. We are here describing the case of a female patient with rumination syndrome where specific points in the history delineated the presence of this illness and helped in appropriate management. The patient became symptom free soon after the diagnosis was reached.
Psychogenic; intractable vomiting; rumination
A number of techniques have been described to reattach the torn distal biceps tendon to the bicipital tuberosity. We report a retrospective analysis of single incision technique using an endobutton fixation in sports persons.
Materials and Methods:
The present series include nine torn distal biceps tendons in eight patients, fixed anatomically to the radial tuberosity with an endobutton by using a single incision surgical technique; seven patients had suffered the injuries during contact sports. The passage of the endobutton was facilitated by using a blunt tipped pin in order to avoid injury to the posterior interosseous nerve. The patients were evaluated by Disabilities of the Arm, Shoulder and Hand (DASH) score and Mayo elbow score.
The average age of the patients was 27.35 years (range 21–42 years). Average follow-up was 41.5 months (range 24–102 months). The final average flexion extension arc was 0°–143°, while the average pronation and supination angles were 77° (range 70°–82°) and 81° (range 78°–85°), respectively at the last followup. All the patients had a Disabilities of the Arm, Shoulder and Hand (DASH) score of 0 and a Mayo elbow score of 100 each. All the seven active sports persons were able to get back to their respective game. There was no nerve injury or any other complication.
The surgical procedure used by us is a simple, safe and reproducible technique giving minimal morbidity and better cosmetic results.
Autograft; biceps tendon; elbow; tendon repair; tendon rupture
Urinary tract infections (UTIs) are amongst the most common infections described in outpatients setting.
A study was conducted to evaluate the uropathogenic bacterial flora and its antimicrobial susceptibility profile among patients presenting to the out-patient clinics of a tertiary care hospital at Jaipur, Rajasthan.
Materials and Methods:
2012 consecutive urine specimens from symptomatic UTI cases attending to the outpatient clinics were processed in the Microbiology lab. Bacterial isolates obtained were identified using biochemical reactions. Antimicrobial susceptibility testing was performed by the Kirby-Bauer disc diffusion method. Extended spectrum beta lactamase (ESBL) production was determined by the double disk approximation test and the Clinical and Laboratory Standards Institute (formerly NCCLS) confirmatory method.
Pathogens were isolated from 346 (17.16%) of the 2012 patients who submitted a urine sample. Escherichia coli was the most frequently isolated community acquired uropathogen accounting for 61.84% of the total isolates. ESBL production was observed in 23.83% of E. coli strains and 8.69% of Klebsiella strains. With the exception of Nitrofurantoin, resistance to agents commonly used as empiric oral treatments for UTI was quite high.
The study revealed E. coli as the predominant bacterial pathogen for the community acquired UTIs in Jaipur, Rajasthan. An increasing trend in the production ESBLs among UTI pathogens in the community was noted. Nitrofurantoin should be used as empirical therapy for primary, uncomplicated UTIs.
Urinary tract infection; outpatients; Escherichia coli
Papillary carcinoma of the breast represents approximately 0.5% of all newly diagnosed cases of breast cancer. The prevalence of both invasive and in situ papillary carcinoma seems to be greater older postmenopausal women, and -in relative terms-in males. Histologic features of the tumor include cellular proliferations surrounding fibrovascular cores, with or without invasion. In this review, characteristics of both in situ and invasive disease are outlined. Immunohistochemical analyses of papillary carcinoma suggest the utility of markers such as smooth muscle myosin heavy chain, calponin, p63 and high molecular weight keratins, which can characterize the myoepithelial cell layer. With respect to radiographic evaluation of papillary carcinoma, ultrasonography is the most extensively studied imaging modality, though magnetic resonance mammography has potential utility. Available data suggest improved outcome for papillary carcinoma as compared to invasive ductal carcinoma. Treatment-related information for patients with papillary carcinoma is limited, and patterns noted in available series suggest a variable approach to this disease. The scarcity of information underscores the need for further treatment- and outcome-related studies in papillary carcinoma of the breast.
papillary; breast carcinoma; male breast cancer; breast ultrasonography; breast magnetic resonance mammography
The objective of this study is to translate and validate the International Restless Leg Syndrome Study Group rating scale (IRLS) in Hindi language.
Materials and Methods:
Thirty one consecutive patients diagnosed of Restless Leg Syndrome (RLS) were included in the study. Control group comprised of 31 subjects not having any symptom of RLS. The scale was procured from MAPI research trust; and, permission for the translation was sought. The translation was done according to the guidelines provided by the publisher. After translation, final version of the scale was applied in both the groups to find out the reliability and clinical validity.
RLS group had a predominance of females, and they were younger than the male counterparts (Age=36.80 ± 10.46 years vs 45.18 ± 8.34 years; t=2.28; P=0.03). There was no difference in the mean age between groups (RLS=39.77 ± 10.44 years vs Non RLS=38.29 ± 11.29 years; t=-0.53; P=0.59). IRLS scores were significantly different between both groups on all items (P<0.001). Translated version showed high reliability (Cronbach's alpha=0.86). IRLS scores were significantly different between both groups on all items (P<0.001).
Hindi version of IRLS is reliable and a clinically valid tool that can be applied in Hindi speaking population.
Hindi translation; International Restless Leg Syndrome Study Group rating scale; Restless Leg Syndrome; translation; validation
Most of the position weight matrix (PWM) based bioinformatics methods developed to predict transcription factor binding sites (TFBS) assume each nucleotide in the sequence motif contributes independently to the interaction between protein and DNA sequence, usually producing high false positive predictions. The increasing availability of TF enrichment profiles from recent ChIP-Seq methodology facilitates the investigation of dependent structure and accurate prediction of TFBSs. We develop a novel Tree-based PWM (TPWM) approach to accurately model the interaction between TF and its binding site. The whole tree-structured PWM could be considered as a mixture of different conditional-PWMs. We propose a discriminative approach, called TPD (TPWM based Discriminative Approach), to construct the TPWM from the ChIP-Seq data with a pre-existing PWM. To achieve the maximum discriminative power between the positive and negative datasets, the cutoff value is determined based on the Matthew Correlation Coefficient (MCC). The resulting TPWMs are evaluated with respect to accuracy on extensive synthetic datasets. We then apply our TPWM discriminative approach on several real ChIP-Seq datasets to refine the current TFBS models stored in the TRANSFAC database. Experiments on both the simulated and real ChIP-Seq data show that the proposed method starting from existing PWM has consistently better performance than existing tools in detecting the TFBSs. The improved accuracy is the result of modelling the complete dependent structure of the motifs and better prediction of true positive rate. The findings could lead to better understanding of the mechanisms of TF-DNA interactions.
mRNA-Seq technology has revolutionized the field of transcriptomics for identification and quantification of gene transcripts not only at gene level but also at isoform level. Estimating the expression levels of transcript isoforms from mRNA-Seq data is a challenging problem due to the presence of constitutive exons.
We propose a novel algorithm (IsoformEx) that employs weighted non-negative least squares estimation method to estimate the expression levels of transcript isoforms. Validations based on in silico simulation of mRNA-Seq and qRT-PCR experiments with real mRNA-Seq data showed that IsoformEx could accurately estimate transcript expression levels. In comparisons with published methods, the transcript expression levels estimated by IsoformEx showed higher correlation with known transcript expression levels from simulated mRNA-Seq data, and higher agreement with qRT-PCR measurements of specific transcripts for real mRNA-Seq data.
IsoformEx is a fast and accurate algorithm to estimate transcript expression levels and gene expression levels, which takes into account short exons and alternative exons with a weighting scheme. The software is available at http://bioinformatics.wistar.upenn.edu/isoformex.
Insomnia is a common problem that is known to occur during depression. However, literature still debates whether insomnia is part of depression or a separate entity.
Materials and Methods:
Subjects presenting with depressive disorder according to DSM-IV-Text Revision criteria were recruited after seeking informed consent. Clinical interview was performed with the help of Mini International Neuropsychiatric Interview Plus. Their demographic data and depression related history were recorded. Depression severity was assessed by using Hamilton Rating Scale for Depression. Diagnosis of insomnia was made with the help of International Classification of Sleep Disorders-2 criteria. Type of insomnia, its duration, and its relationship with depressive illness were specifically asked. If any subject fulfilled criteria for more than one type of insomnia, both were recorded. Statistical analysis was done with the help of statistical package for social sciences (SPSS) version 17.0. χ2 test, independent sample t test, and Pearson's correlation were performed.
A total of 54 subjects were enrolled in this study. Primary insomnia was seen in 40.7% cases and secondary insomnia in 58.8% cases; 27.3% subjects did not experience insomnia along with depressive disorder. In the primary insomnia category, adjustment insomnia was most prevalent (63.6%), and in secondary insomnia group, insomnia due to depressive disorder was most frequent (59.3%). Interestingly, primary insomnia often followed an onset of depressive illness (P=0.04), while secondary insomnia preceded it (c2 =11.1; P=0.004). The presence of either type of insomnias was not influenced by duration of depressive illness, number of depressive episodes, and duration of current depressive episode. On the other hand, duration of insomnia was positively correlated with total duration of depressive illness (P=0.003), number of episodes (P=0.04), and duration of current depressive episode (P<0.001).
Primary insomnia is common in subjects with depression, and it usually follows depressive illness. On the other hand, secondary insomnia often precedes the onset of depressive illness. Duration of insomnia positively correlates with duration and frequency of depressive episodes.
Major depressive disorder; primary insomnia; secondary insomnia
Aims and Objectives:
Translation of the Insomnia Severity Index from English to Hindi and Validation of the Hindi version.
Materials and Methods:
The translation process of the Insomnia Severity Index was initiated after obtaining due permission from the author of the original version of the same. Translation was carried out by using standard translation procedures, such as combined translation, decentering, and pretest method. The final version of the Insomnia Severity Index in Hindi was finally validated. A randomly selected sample size of 65 subjects was enrolled for the purpose of validation and testing the reliability of Hindi version of the Insomnia Severity Index. Insomnia was present in 45 subjects and they constituted the insomnia group. The rest 20 subjects did not have insomnia and were included in the control group. The Hindi version of the Insomnia Severity Index was applied to both the groups.
The total sample constituted of 50.8% males and 49.2% females. The mean age in the control group was 30.8±8.3 years and that in the insomnia group was 40.3±4 years (t=3.04; P=0.001). The translated version of the Insomnia Severity Index showed a reliability of 0.91 (Cronbach's α=0.91). This was not just simple translation, but many of the words were changed to adapt it for the local population.
The Hindi version of the Insomnia Severity Index is a valid and reliable tool that can be administered for the assessment of severity of insomnia.
Hindi; insomnia; insomnia severity index; validation
Kleine–Levin syndrome (KLS) and idiopathic hypersomnia (IH) are primary sleep disorders of unknown etiologies, which often run a chronic course. The common core symptoms of these syndromes are hypersomnolence and sleep drunkenness, with periodic hypersomnolence and hyperphagia being the prominent symptoms of KLS. Psychiatric manifestations are common to both and include irritability, depression, apathy, inattention and poor concentration. Both disorders are diagnosed clinically and no specific laboratory investigation is available to confirm the diagnosis. We present a case highlighting the overlapping of the symptoms of KLS and IH, producing a complex clinical picture.
Hyperphagia; hypersomnolence; idiopathic hypersomnia; Kleine–Levin syndrome; periodic hypersomnolence
The virulence of Pseudomonas aeruginosa is multifactorial and under the control of quorum sensing signals, such as acyl homoserine lactones (AHLs). The importance of these molecules in the establishment of infection has been previously reported. These molecules either improve the virulence potential of P. aeruginosa or modulate the host immune response. To establish the immune modulating potential of quorum sensing signal molecules, previous studies have only used synthetic AHLs. However, there can be differences in the biological properties of synthetic and natural AHLs. The use of naturally extracted AHLs from the culture supernatant of P. aeruginosa is likely to simulate natural conditions more than the use of synthetic AHLs. Therefore, in the present study, the immune modulating potential of synthetic and naturally extracted AHLs was compared using a thymidine uptake assay, immunophenotyping and sandwich ELISA in order to assess mouse T-cell proliferation and production of Th1 and Th2 cytokines. Natural AHLs were able to suppress T-cell proliferation, even at low concentrations, compared to synthetic AHLs. The majority of cells undergoing proliferation were CD4+, as revealed by immunophenotyping. The inhibition of T-cells was stronger with natural AHLs compared to synthetic AHLs. Moreover, the natural AHLs were also able to shift immune responses away from host protective Th1 responses to pathogen protective Th2 responses.
The Q151M multi-drug resistance (MDR) pathway in HIV-1 reverse transcriptase (RT) confers reduced susceptibility to all nucleoside reverse transcriptase inhibitors (NRTIs) excluding tenofovir (TDF). This pathway emerges after long term failure of therapy, and is increasingly observed in the resource poor world, where antiretroviral therapy is rarely accompanied by intensive virological monitoring. In this study we examined the genotypic, phenotypic and fitness correlates associated with the development of Q151M MDR in the absence of viral load monitoring.
Single-genome sequencing (SGS) of full-length RT was carried out on sequential samples from an HIV-infected individual enrolled in ART rollout. The emergence of Q151M MDR occurred in the order A62V, V75I, and finally Q151M on the same genome at 4, 17 and 37 months after initiation of therapy, respectively. This was accompanied by a parallel cumulative acquisition of mutations at 20 other codon positions; seven of which were located in the connection subdomain. We established that fourteen of these mutations are also observed in Q151M-containing sequences submitted to the Stanford University HIV database. Phenotypic drug susceptibility testing demonstrated that the Q151M-containing RT had reduced susceptibility to all NRTIs except for TDF. RT domain-swapping of patient and wild-type RTs showed that patient-derived connection subdomains were not associated with reduced NRTI susceptibility. However, the virus expressing patient-derived Q151M RT at 37 months demonstrated ~44% replicative capacity of that at 4 months. This was further reduced to ~22% when the Q151M-containing DNA pol domain was expressed with wild-type C-terminal domain, but was then fully compensated by coexpression of the coevolved connection subdomain.
We demonstrate a complex interplay between drug susceptibility and replicative fitness in the acquisition Q151M MDR with serious implications for second-line regimen options. The acquisition of the Q151M pathway occurred sequentially over a long period of failing NRTI therapy, and was associated with mutations in multiple RT domains.
Migraine and tension type headache (TTH) are two most common types of primary headaches. Though the International Classification of Headache Disorders-2 (ICHD-2) describes the diagnostic criteria, even then in clinical practice, patients may not respect these boundaries resulting in the difficulty in diagnosis of these pains.
Materials and Methods:
This cross-sectional study involved 50 subjects in each of the two groups – migraine and TTH – after screening for the inclusion and exclusion criteria. Diagnosis was made according to the ICHD-2 criteria. Their clinical history was taken in detail and noted in a semi-structured performa. They were examined for the presence of a number of factors like pericranial tenderness and muscle parafunction. Statistical analysis was done with the help of SPSS v 11.0. To compare the non-parametric issues, chi-square test was run and continuous variables were analyzed using independent sample t test.
In general, migraineurs had progressive illness (χ2=9.45; P=0.002) with increasing severity (χ2=21.86; P<0.001), frequency (χ2=8.5; P=0.04) and duration of each headache episode (χ2=4.45; P=0.03) as compared to TTH subjects. Along with the headache, they more commonly suffered orthostatic pre-syncope (χ2=19.94; P<0.001), palpitations (42%vs.18% among TTH patients; χ2=6.87; P=0.009), nausea and vomiting (68% vs. 6% in TTH; χ2=41.22; P<0.001, and 38% vs. none in TTH; χ2=23.45, P<0.001, respectively), phonophobia (χ2=44.98; P<0.001), photophobia (χ2=46.53; P<0.001), and osmophobia (χ2=15.94; P<0.001). Their pain tended to be aggravated by head bending (χ2=50.17; P<0.001) and exercise (χ2=11.41; P<0.001). Analgesics were more likely to relieve pain in migraineurs (χ2=21.16; P<0.001). In addition, post-headache lethargy was more frequent among the migraineurs (χ2=22.01; P<0.001). On the other hand, stressful situations used to trigger TTH (χ2=9.33; P=0.002) and muscle parafunction was more common in TTH patients (46% vs. 20%; χ2=7.64; P=0.006). All the cranial autonomic symptoms were more common in migraineurs as compared to TTH subjects (conjunctival injection: χ2=10.74, P=0.001; lacrimation: χ2=17.82, P<0.001; periorbital swelling: χ2=23.45, P<0.001; and nasal symptoms: χ2=6.38, P=0.01).
A number of symptoms that are presently not included in the ICHD-2 classification may help in differe-ntiating the migraine from the TTH.
Migraine; symptoms; tension type headache
MPromDb (Mammalian Promoter Database) is a curated database that strives to annotate gene promoters identified from ChIP-seq results with the goal of providing an integrated resource for mammalian transcriptional regulation and epigenetics. We analyzed 507 million uniquely aligned RNAP-II ChIP-seq reads from 26 different data sets that include six human cell-types and 10 distinct mouse cell/tissues. The updated MPromDb version consists of computationally predicted (novel) and known active RNAP-II promoters (42 893 human and 48 366 mouse promoters) from various data sets freely available at NCBI GEO database. We found that 36% and 40% of protein-coding genes have alternative promoters in human and mouse genomes and ∼40% of promoters are tissue/cell specific. The identified RNAP-II promoters were annotated using various known and novel gene models. Additionally, for novel promoters we looked into other evidences—GenBank mRNAs, spliced ESTs, CAGE promoter tags and mRNA-seq reads. Users can search the database based on gene id/symbol, or by specific tissue/cell type and filter results based on any combination of tissue/cell specificity, Known/Novel, CpG/NonCpG, and protein-coding/non-coding gene promoters. We have also integrated GBrowse genome browser with MPromDb for visualization of ChIP-seq profiles and to display the annotations. The current release of MPromDb can be accessed at http://bioinformatics.wistar.upenn.edu/MPromDb/.
We present a case of an iatrogenic left ulnar nerve injury caused during the basilic vein cut down in a 25-year-old woman presenting with a ruptured ectopic pregnancy and requiring an emergency laparotomy. Two months after her discharge from the hospital, the patient presented to the hand surgery clinic with a weak grip strength and paraesthesias in the left hand, diagnosed to be resulting from a deficient ulnar nerve function. Surgical exploration of the nerve showed a complete section of the nerve. End to end repair and anterior transposition of the nerve was done. At 10 months follow up, the patient showed recovery in the flexor digitorum profundus and flexor carpi ulnaris, thus partially improving the grip strength. The patient was still under follow-up at the time this report was prepared.
Trimethylated lysine 27 of histone H3 (H3K27me3) is an epigenetic mark for gene silencing and can be demethylated by the JmjC domain of UTX. Excessive H3K27me3 levels can cause tumorigenesis, but little is known about the mechanisms leading to those cancers. Mutants of the Drosophila H3K27me3 demethylase dUTX display some characteristics of Trithorax group mutants and have increased H3K27me3 levels in vivo. Surprisingly, dUTX mutations also affect H3K4me1 levels in a JmjC-independent manner. We show that a disruption of the JmjC domain of dUTX results in a growth advantage for mutant cells over adjacent wild-type tissue due to increased proliferation. The growth advantage of dUTX mutant tissue is caused, at least in part, by increased Notch activity, demonstrating that dUTX is a Notch antagonist. Furthermore, the inactivation of Retinoblastoma (Rbf in Drosophila) contributes to the growth advantage of dUTX mutant tissue. The excessive activation of Notch in dUTX mutant cells leads to tumor-like growth in an Rbf-dependent manner. In summary, these data suggest that dUTX is a suppressor of Notch- and Rbf-dependent tumors in Drosophila melanogaster and may provide a model for UTX-dependent tumorigenesis in humans.
Alternative promoters that are differentially used in various cellular contexts and tissue types add to the transcriptional complexity in mammalian genome. Identification of alternative promoters and the annotation of their activity in different tissues is one of the major challenges in understanding the transcriptional regulation of the mammalian genes and their isoforms. To determine the use of alternative promoters in different tissues, we performed ChIP-seq experiments using antibody against RNA Pol-II, in five adult mouse tissues (brain, liver, lung, spleen and kidney). Our analysis identified 38 639 Pol-II promoters, including 12 270 novel promoters, for both protein coding and non-coding mouse genes. Of these, 6384 promoters are tissue specific which are CpG poor and we find that only 34% of the novel promoters are located in CpG-rich regions, suggesting that novel promoters are mostly tissue specific. By identifying the Pol-II bound promoter(s) of each annotated gene in a given tissue, we found that 37% of the protein coding genes use alternative promoters in the five mouse tissues. The promoter annotations and ChIP-seq data presented here will aid ongoing efforts of characterizing gene regulatory regions in mammalian genomes.