B P Chowdhary

Qatar University, Ad Dawḩah, Ad Dawḩah, Qatar

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Publications (201)562.16 Total impact

  • S Ghosh · P J Das · F Avila · B K Thwaits · B P Chowdhary · T Raudsepp ·
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    ABSTRACT: Balanced autosomal translocations are a known cause for repeated early embryonic loss (REEL) in horses. In most cases, carriers of such translocations are phenotypically normal, but the chromosomal aberration negatively affects gametogenesis giving rise to both genetically balanced and unbalanced gametes. The latter, if involved in fertilization, result in REEL, whereas gametes with the balanced form of translocation will pass the defect into next generation. Therefore, in order to reduce the incidence of REEL, identification of translocation carriers is critical. Here, we report about a phenotypically normal 3-year-old Arabian mare that had repeated resorption of conceptuses prior to day 45 of gestation and was diagnosed with REEL. Conventional and molecular cytogenetic analyses revealed that the mare had normal chromosome number 64,XX but carried a non-mosaic and non-reciprocal autosomal translocation t(4;10)(q21;p15). This is a novel translocation described in horses with REEL and the first such report in Arabians. Previous cases of REEL due to autosomal translocations have exclusively involved Thoroughbreds. The findings underscore the importance of routine cytogenetic screening of breeding animals.
    Reproduction in Domestic Animals 11/2015; DOI:10.1111/rda.12636 · 1.52 Impact Factor
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    ABSTRACT: Cryptorchidism (CO) is the most common non-lethal congenital disorder in male horses and negatively impacts the economy of the horse industry globally. The composite genetic component of CO is as yet poorly understood though findings in human suggest the involvement of DNA copy number variants (CNVs). Here we conducted genome-wide CNV analysis by array comparative genomic hybridization in normal and CO horses. We revealed a 200 kb homozygous deletion in chromosome 29 in some CO horses. Homozygosity of the CNV was confirmed by PCR and fluoresence in situ hybridization (FISH). The deletion disrupted a cluster of AKR1C genes known to be involved in sex hormone metabolism and sexual development. Further analysis by FISH in selected CO and control horses showed that the deletion is homozygous in some CO horses and heterozygous in others, while no deletion was detected in controls. The findings suggested potentially causative relationship between the CNV and equine CO. Therefore, attempts were made to precisely demarcate deletion breakpoints and design a PCR test for population analysis to identify homozygous and heterozygous carriers, and ascertain genotype-phenotype association. We observed that the deletion landscape is complex and that the reference genome might have mis-assemblies in the region. Currently, re-sequencing of the CNV region in chromosome 29 is in progress. The goal is to improve the assembly and annotation of the AKR1C-region and develop a diagnostic test for detecting mutation carriers. The biomedical importance of the findings will potentially extend to other domestic animals and humans.
    Plant and Animal Genome Workshop, San Diego, CA; 01/2015
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    ABSTRACT: We constructed a 400K WG tiling oligoarray for the horse and applied it for the discovery of copy number variations (CNVs) in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Probes on the array represented 18,763 autosomal and X-linked genes, and intergenic, sub-telomeric and chrY sequences. We identified 258 CNV regions (CNVRs) across all autosomes, chrX and chrUn, but not in chrY. CNVs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred reference. The Przewalski horse was similar to native ponies and draft breeds. The majority of CNVRs involved genes, while 20% were located in intergenic regions. Similar to previous studies in horses and other mammals, molecular functions of CNV-associated genes were predominantly in sensory perception, immunity and reproduction. The findings were integrated with previous studies to generate a composite genome-wide dataset of 1476 CNVRs. Of these, 301 CNVRs were shared between studies, while 1174 were novel and require further validation. Integrated data revealed that to date, 41 out of over 400 breeds of the domestic horse have been analyzed for CNVs, of which 11 new breeds were added in this study. Finally, the composite CNV dataset was applied in a pilot study for the discovery of CNVs in 6 horses with XY disorders of sexual development. A homozygous deletion involving AKR1C gene cluster in chr29 in two affected horses was considered possibly causative because of the known role of AKR1C genes in testicular androgen synthesis and sexual development. While the findings improve and integrate the knowledge of CNVs in horses, they also show that for effective discovery of variants of biomedical importance, more breeds and individuals need to be analyzed using comparable methodological approaches.
    PLoS Genetics 10/2014; 10(10):e1004712. DOI:10.1371/journal.pgen.1004712 · 7.53 Impact Factor
  • Samantha M Steelman · Philip Johnson · Amy Jackson · James Schulze · Bhanu P Chowdhary ·
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    ABSTRACT: Acute laminitis is an inflammatory disease of the equine foot that often occurs secondary to sepsis or systemic inflammation associated with gastrointestinal disease. It has been suggested that laminitis is similar to multiple organ dysfunction syndrome (MODS) in humans, although in horses the weight-bearing laminar epithelium of the foot appears to be the tissue most sensitive to insult and the first "organ" to fail. Metabolomics performed on serum samples collected before (CON) and after (LMN) experimental induction of gastrointestinal-associated sepsis in 6 horses detected 1177 metabolites of both mammalian and bacterial origin in equine serum. Network and correlation analyses suggested a dysregulation of fatty acid metabolism in the LMN group, as well as an accumulation of organic acids such as lactate. Furthermore, concentrations of the amino acid citrulline were decreased in LMN samples from all study animals, suggesting that citrulline might be useful as a biomarker to identify critically ill animals that are at risk of developing laminitis. We therefore established normal ranges of plasma citrulline concentrations in a separate group of horses (n = 36) and tested the ability of citrulline to predict adverse outcomes (laminitis or death) in critically ill horses (n = 23). Plasma citrulline was significantly lower in critically ill horses that went on to experience adverse outcomes (n = 6). Further study is required to accurately determine a diagnostic cutoff, but the present data are suggestive of the predictive value of citrulline as a biomarker for laminar failure in equine sepsis.
    Physiological Genomics 03/2014; 46(10). DOI:10.1152/physiolgenomics.00180.2013 · 2.37 Impact Factor
  • S. Ghosh · P.J. Das · C. Arnold · J. Jaxheimer · D.D. Varner · B.P. Chowdhary · T. Raudsepp ·

    Journal of Equine Veterinary Science 01/2014; 34(1):29. DOI:10.1016/j.jevs.2013.10.015 · 0.87 Impact Factor
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    ABSTRACT: A Quarter Horse gelding presented with pathology consistent with hereditary equine regional dermal asthenia (HERDA) but without the familial association typically present with this disease. Grossly, lesions exhibited either a firm, scar-like appearance or a potential space between the superficial and deep dermis. Both lesioned and non-lesioned skin showed evidence of edema and collagen fragmentation, whereas lesions were also characterized by hemorrhage and inflammation. Genetic testing was performed by three independent laboratories, each using different methods to detect the mutation described in the PPIB gene, previously shown to be associated with HERDA. No mutations in the PPIB gene were revealed by genetic testing, either at the known location of the point mutation or at any other location in the coding sequence. These findings are suggestive of a diagnosis of HERDA or hyperelastosis cutis in the absence of the well-described, putatively causative mutation in the PPIB gene. We propose that, whereas HERDA refers specifically to a familial disease caused by a mutation in the PPIB gene, similar symptoms may in fact be caused by a syndrome resulting from either inherited or spontaneous mutations in any of a number of collagen-processing genes. We conclude that Ehlers-Danlos syndrome be diagnosed in horses of any breed with HERDA-like pathology without the causative mutation.
    Journal of Equine Veterinary Science 12/2013; 34(4). DOI:10.1016/j.jevs.2013.10.178 · 0.87 Impact Factor

  • Proceedings of the National Academy of Sciences 10/2013; 110(46). DOI:10.1073/pnas.1315122110 · 9.67 Impact Factor

  • Journal of Equine Veterinary Science 10/2013; 33(10):855. DOI:10.1016/j.jevs.2013.08.020 · 0.87 Impact Factor
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    P J Das · D K Mishra · S Ghosh · F Avila · G A Johnson · B P Chowdhary · T Raudsepp ·
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    ABSTRACT: The pseudoautosomal region (PAR) has important biological functions in spermatogenesis, male fertility and early development. Even though pig (Sus scrofa, SSC) is an agriculturally and biomedically important species, and its genome is sequenced, current knowledge about the porcine PAR is sparse. Here we defined the PAR in SSCXp/Yp by demarcating the sequence of the pseudoautosomal boundary at X:6,743,567 bp in intron 3-4 of SHROOM2 and showed that SHROOM2 is truncated in SSCY. Cytogenetic mapping of 20 BAC clones containing 15 PAR and X-specific genes revealed that the pig PAR is largely collinear with other mammalian PARs or Xp terminal regions. The results improved the current SSCX sequence assembly and facilitated distinction between the PAR and X-specific genes to study their expression in adult and embryonic tissues. A pilot analysis showed that the PAR genes are expressed at higher levels than X-specific genes during early development, whereas the expression of PAR genes was higher at day 60 compared to day 26, and higher in embryonic tissues compared to placenta. The findings advance the knowledge about the comparative organization of the PAR in mammals and suggest that the region might have important functions in early development in pigs.
    Cytogenetic and Genome Research 05/2013; 141(1). DOI:10.1159/000351310 · 1.56 Impact Factor
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    Priyanka Kachroo · Ivan Ivanov · Ashley G Seabury · Mei Liu · Bhanu P Chowdhary · Noah D Cohen ·
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    ABSTRACT: Rhodococcus equi is an intracellular bacterium primarily known as an equine pathogen that infects young foals causing a pyogranulomatuous pneumonia. The molecular mechanisms mediating the immune response of foals to R. equi are not fully elucidated. Hence, global genomic high-throughput tools like gene expression microarrays might identify age-related gene expression signatures and molecular pathways that contribute to the immune mechanisms underlying the inherent susceptibility of foals to disease caused by R. equi. The objectives of this study were 2-fold: 1) to compare the expression profiles at specific ages of blood leukocytes from foals stimulated with virulent R. equi with those of unstimulated leukocytes; and, 2) to characterize the age-related changes in the gene expression profile associated with blood leukocytes in response to stimulation with virulent R. equi. Peripheral blood leukocytes were obtained from 6 foals within 24 hours (h) of birth (day 1) and 2, 4, and 8 weeks after birth. The samples were split, such that half were stimulated with live virulent R. equi, and the other half served as unstimulated control. RNA was extracted and the generated cDNA was labeled with fluorescent dyes for microarray hybridizations using an equine microarray. Our findings suggest that there is age-related differential expression of genes involved in host immune response and immunity. We found induction of genes critical for host immunity against pathogens (MHC class II) only at the later time-points (compared to birth). While it appears that foals up to 8-weeks of age are able to initiate a protective inflammatory response against the bacteria, relatively decreased expression of various other immune-related genes points toward inherent diminished immune responses closer to birth. These genes and pathways may contribute to disease susceptibility in foals if infected early in life, and might thus be targeted for developing preventative or therapeutic strategies.
    PLoS ONE 05/2013; 8(5):e62879. DOI:10.1371/journal.pone.0062879 · 3.23 Impact Factor
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    ABSTRACT: Chronic equine laminitis causes persistent pain and lameness in affected animals and often necessitates euthanasia when pain management strategies become ineffective. Published studies as well as anecdotal reports suggest that this chronic inflammatory disease is associated with systemic alterations in immune responsiveness, perhaps involving an autoimmune component. We investigated this broad hypothesis by measuring a variety of immune indicators in healthy control horses (CON) and horses with chronic laminitis (LMN). We found that white blood cells from LMN horses produced more IFN? than did cells from CON horses when stimulated in vitro with polyinosinic-polycytidylic acid [poly(I:C)], possibly due to an elevated number of circulating monocytes. No differences between groups were observed in plasma concentrations of IgG, IgA, IgM, IgE, or rheumatoid factor. Laminar tissue from LMN horses expressed elevated levels of keratinocyte damage-related genes as well as inflammatory cytokines and chemokines, which corresponded with a modest amount of neutrophil infiltration as shown by histological staining of fixed tissue and accumulation of neutrophil elastase protein. Taken together, our results do not support the hypothesis of an autoimmune component in chronic laminitis, although the strong induction of neutrophil chemokines and the presence of tissue neutrophils suggests that this cell type is likely involved in perpetuating the inflammation and tissue damage associated with this disease.
    Veterinary Immunology and Immunopathology 03/2013; 153(3). DOI:10.1016/j.vetimm.2013.03.001 · 1.54 Impact Factor
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    ABSTRACT: Mature mammalian sperm contain a complex population of RNAs some of which might regulate spermatogenesis while others probably play a role in fertilization and early development. Due to this limited knowledge, the biological functions of sperm RNAs remain enigmatic. Here we report the first characterization of the global transcriptome of the sperm of fertile stallions. The findings improved understanding of the biological significance of sperm RNAs which in turn will allow the discovery of sperm-based biomarkers for stallion fertility. The stallion sperm transcriptome was interrogated by analyzing sperm and testes RNA on a 21,000-element equine whole-genome oligoarray and by RNA-seq. Microarray analysis revealed 6,761 transcripts in the sperm, of which 165 were sperm-enriched, and 155 were differentially expressed between the sperm and testes. Next, 70 million raw reads were generated by RNA-seq of which 50% could be aligned with the horse reference genome. A total of 19,257 sequence tags were mapped to all horse chromosomes and the mitochondrial genome. The highest density of mapped transcripts was in gene-rich ECA11, 12 and 13, and the lowest in gene-poor ECA9 and X; 7 gene transcripts originated from ECAY. Structural annotation aligned sperm transcripts with 4,504 known horse and/or human genes, rRNAs and 82 miRNAs, whereas 13,354 sequence tags remained anonymous. The data were aligned with selected equine gene models to identify additional exons and splice variants. Gene Ontology annotations showed that sperm transcripts were associated with molecular processes (chemoattractant-activated signal transduction, ion transport) and cellular components (membranes and vesicles) related to known sperm functions at fertilization, while some messenger and micro RNAs might be critical for early development. The findings suggest that the rich repertoire of coding and non-coding RNAs in stallion sperm is not a random remnant from spermatogenesis in testes but a selectively retained and functionally coherent collection of RNAs.
    PLoS ONE 02/2013; 8(2):e56535. DOI:10.1371/journal.pone.0056535 · 3.23 Impact Factor
  • Terje Raudsepp · Nandina Paria · Bhanu P. Chowdhary ·
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    ABSTRACT: This chapter contains sections titled: Introduction Cytogenetics Molecular Probes Maps The Pseudoautosomal Region (PAR) Disorders Polymorphism and Population Studies Y chromosome in Other Equids and Perissodactyls Concluding Remarks Acknowledgments References
    Equine Genomics, 02/2013: pages 73-92; , ISBN: 9780813815633
  • Bhanu P. Chowdhary ·
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    ABSTRACT: This chapter contains sections titled: Nuclear Genome of the Horse Mitochondrial Genome of the Horse References
    Equine Genomics, 02/2013: pages 1-9; , ISBN: 9780813815633
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    ABSTRACT: Impaired acrosomal reaction (IAR) of sperm causes male subfertility in humans and animals. Despite compelling evidence about the genetic control over acrosome biogenesis and function, the genomics of IAR is as yet poorly understood, providing no molecular tools for diagnostics. Here we conducted Equine SNP50 Beadchip genotyping and GWAS using 7 IAR-affected and 37 control Thoroughbred stallions. A significant (P<6.75E-08) genotype-phenotype association was found in horse chromosome 13 in FK506 binding protein 6 (FKBP6). The gene belongs to the immunophilins FKBP family known to be involved in meiosis, calcium homeostasis, clathrin-coated vesicles, and membrane fusions. Direct sequencing of FKBP6 exons in cases and controls identified SNPs g.11040315G>A and g.11040379C>A (p.166H>N) in exon 4 that were significantly associated with the IAR phenotype both in the GWAS cohort (n = 44) and in a large multi-breed cohort of 265 horses. All IAR stallions were homozygous for the A-alleles, while this genotype was found only in 2% of controls. The equine FKBP6 was exclusively expressed in testis and sperm and had 5 different transcripts, of which 4 were novel. The expression of this gene in AC/AG heterozygous controls was monoallelic, and we observed a tendency for FKBP6 up-regulation in IAR stallions compared to controls. Because exon 4 SNPs had no effect on the protein structure, it is likely that FKBP6 relates to the IAR phenotype via regulatory or modifying functions. In conclusion, FKBP6 was considered a susceptibility gene of incomplete penetrance for IAR in stallions and a candidate gene for male subfertility in mammals. FKBP6 genotyping is recommended for the detection of IAR-susceptible individuals among potential breeding stallions. Successful use of sperm as a source of DNA and RNA propagates non-invasive sample procurement for fertility genomics in animals and humans.
    PLoS Genetics 12/2012; 8(12):e1003139. DOI:10.1371/journal.pgen.1003139 · 7.53 Impact Factor
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    Samantha M Steelman · Bhanu P Chowdhary · Scot Dowd · Jan Suchodolski · Jan E Jane Ka ·
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    ABSTRACT: Background The nutrition and health of horses is closely tied to their gastrointestinal microflora. Gut bacteria break down plant structural carbohydrates and produce volatile fatty acids, which are a major source of energy for horses. Bacterial communities are also essential for maintaining gut homeostasis and have been hypothesized to contribute to various diseases including laminitis. We performed pyrosequencing of 16S rRNA bacterial genes isolated from fecal material to characterize hindgut bacterial communities in healthy horses and those with chronic laminitis. Results Fecal samples were collected from 10 normal horses and 8 horses with chronic laminitis. Genomic DNA was extracted and the V4-V5 segment of the 16S rRNA gene was PCR amplified and sequenced on the 454 platform generating a mean of 2,425 reads per sample after quality trimming. The bacterial communities were dominated by Firmicutes (69.21% control, 56.72% laminitis) and Verrucomicrobia (18.13% control, 27.63% laminitis), followed by Bacteroidetes, Proteobacteria, and Spirochaetes. We observed more OTUs per individual in the laminitis group than the control group (419.6 and 355.2, respectively, P = 0.019) along with a difference in the abundance of two unassigned Clostridiales genera (P = 0.03 and P = 0.01). The most abundant bacteria were Streptococcus spp., Clostridium spp., and Treponema spp.; along with unassigned genera from Subdivision 5 of Verrucomicrobia, Ruminococcaceae, and Clostridiaceae, which together constituted ~ 80% of all OTUs. There was a high level of individual variation across all taxonomic ranks. Conclusions Our exploration of the equine fecal microflora revealed higher bacterial diversity in horses with chronic laminitis and identification of two Clostridiales genera that differed in abundance from control horses. There was large individual variation in bacterial communities that was not explained in our study. The core hindgut microflora was dominated by Streptococcus spp., several cellulytic genera, and a large proportion of uncharacterized OTUs that warrant further investigation regarding their function. Our data provide a foundation for future investigations of hindgut bacterial factors that may influence the development and progression of chronic laminitis.
    BMC Veterinary Research 11/2012; 8(1):231. DOI:10.1186/1746-6148-8-231 · 1.78 Impact Factor
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    Jan Janecka · Bhanu Chowdhary · William Murphy ·
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    ABSTRACT: Sequence evolution behaves in a relatively consistent manner, leading to one of the fundamental paradigms in biology, the existence of a 'molecular clock'. The molecular clock can be distilled to the concept of accumulation of substitutions, through time yielding a stable rate from which we can estimate lineage divergence. Over the last 50 years, evolutionary biologists have obtained an in-depth understanding of this clock's nuances. It has been fine-tuned by taking into account the vast heterogeneity in rates across lineages and genes, leading to 'relaxed' molecular clock methods for timetree reconstruction. Sequence rate varies with life history traits including body size, generation time and metabolic rate, and we review recent studies on this topic. However, few studies have explicitly examined correlates between molecular evolution and morphological evolution. The patterns observed across diverse lineages suggest that rates of molecular and morphological evolution are largely decoupled. We discuss how identifying the molecular mechanisms behind rapid functional radiations are central to understanding evolution. The vast functional divergence within mammalian lineages that have relatively 'slow' sequence evolution refutes the hypotheses that pulses in diversification yielding major phenotypic change are the result of steady accumulation of substitutions. Patterns rather suggest phenotypic divergence is likely caused by regulatory alterations mediated through mechanisms such as insertions/deletions in functional regions. These can rapidly arise and sweep to fixation faster than predicted from a lineage's sequence neutral substitution rate, enabling species to leapfrog between phenotypic 'islands'. We suggest research directions that could illuminate mechanisms behind the functional diversity we see today.
    Journal of Biosciences 11/2012; 37(5):897-909. DOI:10.1007/s12038-012-9254-y · 2.06 Impact Factor
  • Samantha M Steelman · Bhanu P Chowdhary ·
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    ABSTRACT: Background Equine laminitis is a devastating disease that causes severe pain in afflicted horses and places a major economic burden on the horse industry. In acute laminitis, the disintegration of the dermal-epidermal junction can cause the third phalanx to detach from the hoof wall, leaving the horse unable to bear weight on the affected limbs. Horses that survive the acute phase transition into a chronic form of laminitis, which is often termed “founder”. Some evidence suggests that chronic laminar inflammation might be associated with alterations in the endocrine and immune systems. We investigated this broad hypothesis by using DIGE to assess global differences in the plasma proteome between horses with chronic laminitis and controls. Results We identified 16 differentially expressed proteins; the majority of these were involved in the interrelated coagulation, clotting, and kininogen cascades. Clinical testing of functional coagulation parameters in foundered horses revealed a slight delay in prothrombin (PT) clotting time, although most other indices were within normal ranges. Upregulation of the intestinal apolipoprotein APOA-IV in horses with chronic laminitis was confirmed by western blot. Conclusions Our results support the hypothesis that localized laminar inflammation may be linked to systemic alterations in immune regulation, particularly in the gastrointestinal system. Gastrointestinal inflammation has been implicated in the development of acute laminitis but has not previously been associated with chronic laminitis.
    BMC Veterinary Research 09/2012; 8(1):179. DOI:10.1186/1746-6148-8-179 · 1.78 Impact Factor

Publication Stats

6k Citations
562.16 Total Impact Points


  • 2014
    • Qatar University
      Ad Dawḩah, Ad Dawḩah, Qatar
  • 2001-2014
    • Texas A&M University
      • • Department of Large Animal Clinical Sciences
      • • Department of Veterinary Integrative Biosciences
      College Station, Texas, United States
  • 2009
    • Mississippi State University
      • College of Veterinary Medicine
      Mississippi, United States
  • 2006
    • Alabama A & M University
      Huntsville, Alabama, United States
  • 1989-1999
    • Swedish University of Agricultural Sciences
      • Department of Animal Breeding and Genetics
      Uppsala, Uppsala, Sweden
  • 1998
    • Uppsala Monitoring Centre
      Uppsala, Uppsala, Sweden