Publications by authors named "Aleem Ahmed Khan"

34 Publications

Intensive Poultry Farming Practices Influence Antibiotic Resistance Profiles in Inhabiting Nearby Soils.

Infect Drug Resist 2021 29;14:4511-4516. Epub 2021 Oct 29.

Dr. Ghulam Nabi Chaudhry Laboratory of Microbial Technologies, Department of Microbiology and Molecular Genetics, Institute of Pure and Applied Biology, Bahauddin Zakariya University, Multan, Pakistan.

Background: The drastic increase in use of antibiotics as a mandatory part of production in poultry and livestock has led to the development of bacterial resistance against antibiotics. The spread of resistant bacteria from poultry to humans increases the risk of treatment failure by antibiotics because of resistance genes transfer.

Study Objective: The objective of the study was to estimate and compare the resistance profile collected from areas around the poultry farm premises and areas at least 500 meters away from the nearest poultry farm. We studied the effect of antibiotic usage in farms on the bacterial profile present in the upper layer of soil.

Methodology: A total of 1,200 moist soil samples were collected from areas within a 25 meters range of poultry farms and areas that had no poultry farms in its 500 meters vicinity. was cultured and isolated. The antibiotic susceptibility profile was carried out by Kirby-Bauer disc diffusion method and results were analyzed according to CLSI guidelines. Statistical analysis was carried out to check the significance of results.

Results: A total of 300 isolates were isolated, among which 140 isolates were isolated from areas around the poultry farm premises and had higher prevalence of antibiotic resistance. A total of 160 isolates were isolated from areas outside the poultry farm range. Resistance was not as high as in the isolates from around the farm. The ESBL production was higher in the isolates that were in close contact with the poultry farm as compared to the isolates away from the farm.

Conclusion: Use of antibiotics in the poultry farm for production significantly increases the resistance in bacterial strains present in the upper layer of soil around the poultry farm within at least a 25 meter range.
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http://dx.doi.org/10.2147/IDR.S324055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565894PMC
October 2021

Investigations on Acinetophage, QAB 3.4, Targeting Extensively Drug-Resistant Isolates.

Infect Drug Resist 2021 15;14:4261-4269. Epub 2021 Oct 15.

Dr. Ghulam Nabi Chaudhry Laboratory of Microbial Technologies, Department of Microbiology and Molecular Genetics, Institute of Pure and Applied Biology, Bahauddin Zakariya University, Multan, Pakistan.

Purpose: Drug resistance against antimicrobials is on the rise at alarmingly high rates. is one of the six ESKAPE pathogens which are a significant "one health" issue. Clinical isolates of exhibit MDR phenotype mostly and infrequently the XDR and PDR phenotype. As a result, these infections have one of the highest mortality rates in hospitals. Alternative therapies are urgently needed.

Methods: Various phages were enriched against XDR clinical strain of . A potent phage, QAB 3.4, was further tested against 100 clinical strains. Because of its broad lytic activity, it was further tested for stability, resistance development and as an infection control agent.

Results: Phage QAB 3.4 showed broad lytic activity against 100 MDR and XDR clinical isolates representing a wide diversity of infection sites. Assays conducted to document the phage's stability, and ability of clinical isolates to develop resistance against it, showed promising outcomes for its potential use in clinical applications. Phage QAB 3.4 was able to eradicate from pre-inoculated solid surfaces. It provides a proof of concept that phages can be used as environmentally friendly infection control agents.

Conclusion: We propose the phage QAB 3.4 is a promising candidate for further pre-clinical and clinical studies to test its biosafety and efficacy.
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http://dx.doi.org/10.2147/IDR.S307494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526514PMC
October 2021

Biofabrication of allogenic bone grafts using cellularized amniotic scaffolds for application in efficient bone healing.

Tissue Cell 2021 Dec 25;73:101631. Epub 2021 Aug 25.

Central Laboratory for Stem Cell Research & Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, 500058, Telangana, India. Electronic address:

Introduction: The reconstruction/regeneration of human bone injuries/defects represents a crucial challenge due to the lack of suitable bio/immune compatible and implantable biological grafts. The available strategies represent implications of several types of grafting materials in the form of metals, synthetic, and various kinds of biological scaffolds; however, the lack of appropriate biological components required for activating and enhancing repair mechanisms at the lesion-site limits their wider applicability.

Methods: In this study, a unique approach for generating human osteogenic implantable grafts was developed using biofabrication technology. Using a gradient change of detergents and continuous agitation, developed a unique technique to generate completely cell-free amnion and chorion scaffolds. The absence of cellular components and integrity of biological and mechanical cues within decellularized human amnion (D-HAM) and chorion (D-HCM) were evaluated and compared with fresh membranes. Allogenic bone grafts were prepared through induction of human mesenchymal stem cells (hMSCs) into osteogenic cells on D-HAM and D-HCM and evaluated for their comparative behavior at the cellular, histological and molecular levels.

Results: The common decellularization process resulted in an efficient way to generate D-HAM and D-HCM while retaining their intact gross-anatomical architecture, surface morphology, extracellular matrix components, and mechanical properties. Both these scaffolds supported better growth of human umbilical cord blood derived MSCs as well as osteogenic differentiation. Comparative investigation revealed better growth rate and differentiation on D-HCM compared to D-HAM and control conditions.

Conclusion: D-HCM could be used as a better choice for producing suitable allogenic bone grafts for efficient bone healing applications.
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http://dx.doi.org/10.1016/j.tice.2021.101631DOI Listing
December 2021

Genotyping simplified: rationally designed antisense oligonucleotide-mediated PCR amplification-free colorimetric sensing of viral RNA in HCV genotypes 1 and 3.

Analyst 2021 Jul;146(15):4767-4774

Department of Biological Sciences, BITS Pilani Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal, Hyderabad-500078, India.

Molecular diagnosis of viral genotyping devoid of polymerase chain reaction (PCR) amplification in clinical cohorts has hitherto been challenging. Here we present a simplified molecular diagnostic strategy for direct genotyping of hepatitis C virus (HCV) 1 and 3 (prevalent worldwide) using a combination of rationally designed genotype-specific antisense oligonucleotides (ASOs) and plasmonic gold nanoparticles. The ASOs specific to genotypes 1 and 3 have been designed from the nonstructural region 5A (NS5A) of the viral genome using the ClustalW multiple sequence alignment tool. A total of 79 clinical samples including 18 HCV genotype 1, 18 HCV genotype 3, one HIV positive, one HBV positive, and 41 healthy controls have been tested against both the designed ASOs. The study reveals 100% specificity and sensitivity with the employed samples and thereby opens up new avenues for PCR-free direct genotyping of other viruses as well, through the rational design of ASOs.
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http://dx.doi.org/10.1039/d1an00590aDOI Listing
July 2021

Status of Vitamin D Receptor Gene Polymorphism and 25-Hydroxy Vitamin D Deficiency with Essential Hypertension.

Indian J Clin Biochem 2021 Jun 15:1-7. Epub 2021 Jun 15.

Central Laboratory for Stem Cell Research and Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, Telangana 500058 India.

Essential hypertension (EH) is a multifactorial and complex disease with high rate of incidence and associated co-morbidities. Previous studies do not provide unanimous results for the risk of hypertension and association with Fok I genotype frequency and serum vitamin D levels. Hence, this study was undertaken to determine the status of Fok I vitamin D receptor (VDR) gene polymorphism along with vitamin D levels and blood pressure in patients with EH. Four hundred (200 controls and 200 cases of essential hypertension) participants from general Indian population were enrolled in this study. Peripheral blood samples were collected for genotyping Fok I-VDR gene polymorphism using PCR-RFLP method whereas 25-OH vitamin D levels in serum were quantified using high performance liquid chromatography (HPLC). Significantly reduced 25-OH vitamin D levels were observed in patients with EH (24.04 ± 8.62 vs 50.46 ± 15.46) compared to control subjects ( = 0.0001). Homozygous recessive genotype 'ff' frequency was increased by 8.06 fold (CI: 3.71-17.47,  = 0.0001) in patients with EH compared to dominant 'FF' genotype frequency. In conclusion, recessive 'ff' genotype frequency correlates with reduced serum vitamin D levels and results in significantly increased systolic and diastolic blood pressures leading to predisposition of EH.
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http://dx.doi.org/10.1007/s12291-021-00984-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203720PMC
June 2021

Correlation between antibiotic resistance and phylogenetic types among multidrug-resistant isolated from urinary tract infections.

Iran J Basic Med Sci 2021 Mar;24(3):400-407

PCSIR Laboratories Islamabad, Pakistan.

Objectives: Emergence of multidrug resistance has reduced the choice of antimicrobial regimens for UTIs. To understand the association of phenotype and genotype among uropathogens.

Materials And Methods: Six hundred and twenty-eight (628) urine samples were collected and analyzed. Antibiotic sensitivity pattern was determined by the Kirby-Bauer Disc Diffusion Method and minimum inhibitory concentration (MIC) was tested by the E test. Fluoroquinolone resistant mutations in QRDR of and , phylogenetic groups, and PAI subtype were detected by PCR.

Results: Most prevalent uropathogens were (53.2%) followed by (21%). Multidrug- resistance was observed in > 50% cases for third-generation cephalosporins and ciprofloxacin and lowest in meropenem. (66.2%) and (64.4%) were extended-spectrum β-lactamases (ESBLs) producers. MIC to trimethoprim-sulfamethoxazole was highest in (>1024 µg/ml). In 80 (24%) of the 334 isolates analyzed in detail, 54 fluoroquinolones (FQ) resistant isolates carried mutations (S83L, D87N, S80I, E84V) in QRDR of and . Out of 54 FQ-resistant isolates, 43 (79.6%) isolates belonged to the phylogenetic group B2, and 11(20.4%) belonged to group D. Isolates belonged to group B2, 38 (88.4%) of the 43 isolates carried PAI subtype IIa and high frequency of mutation E84V in was detected in 37 (97.4%). Other mutations, such as S80I, S83L in and D87N in were found in all resistant isolates.

Conclusion: Correlations between phenotype and genotype provided a basis to understand the resistance development in uropathogens, and PAI subtyping indicated that belonged to the B2 group.
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http://dx.doi.org/10.22038/ijbms.2021.47095.10865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087846PMC
March 2021

Biofabrication of cell-laden allografts of goat urinary bladder scaffold for organ reconstruction/regeneration.

Tissue Cell 2020 Dec 28;67:101443. Epub 2020 Sep 28.

Central Laboratory for Stem Cell Research and Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad 500058, Telangana, India. Electronic address:

Introduction: Bladder dysfunction has been considered as one of the most critical health conditions with no proper treatment. Current therapeutic approaches including enterocystoplasty have several limitations. Hence, biofabrication of cell-laden biological allografts using decellularized Goat urinary bladder scaffolds for organ reconstruction/regeneration was major objective of this study.

Materials And Methods: An efficient method for decellularization of Goat urinary bladder (N = 3) was developed by perfusion of gradient change of detergents through ureter. The retention of organ architecture, extracellular matrix composition, mechanical properties and removal of cellular components was characterized using histological, cellular and molecular analysis. Further, mesenchymal stem cells (MSCs) from human umbilical cord blood (UCB) were used for preparing biological construct of decellularized urinary bladder (DUB) scaffolds to augment the urinary bladder reconstruction/regeneration.

Results: The decellularization method adopted in this study generated completely DUB scaffolds within 10 h at 100 mm Hg pressure and constant flow rate of 1 mL/min. The DUB scaffold retains organ architecture, ECM composition, and mechanical strength. No significant amount of residual nucleic acid was observed post-decellularization. Furthermore, MSCs derived from human UCB engrafted and proliferated well on DUB scaffolds in highly aligned manner under xeno-free condition.

Conclusion: Biofabricated humanized urinary bladder constructs provides xeno-free allografts for future application in augmenting urinary bladder reconstruction/regeneration with further development.
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http://dx.doi.org/10.1016/j.tice.2020.101443DOI Listing
December 2020

Engineering bio-mimetic humanized neurological constructs using acellularized scaffolds of cryopreserved meningeal tissues.

Mater Sci Eng C Mater Biol Appl 2019 Sep 12;102:34-44. Epub 2019 Apr 12.

Central Laboratory for Stem Cell Research and Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad 500058, Telangana, India; Dr Habeebullah Life Sciences, Attapur, Hyderabad, Telangana, India. Electronic address:

Spinal cord injury (SCI) is one of the most precarious conditions which have been one of the major reasons for continuous increasing mortality rate of SCI patients. Currently, there is no effective treatment modality for SCI patients posing major threat to the scientific and medical community. The available strategies don't mimic with the natural processes of nervous tissues repair/regeneration and majority of the approaches may induce the additional fibrotic or immunological response at the injury site and are not readily available on demand. To overcome these hurdles, we have developed a ready to use bioengineered human functional neurological construct (BHNC) for regenerative applications in SCI defects. We used cryopreserved meningeal tissues (CMT) for bioengineering these neurological constructs using acellularization and repopulation technology. The technology adopted herein generates intact neurological scaffolds from CMT and retains several crucial structural, biochemical and mechanical cues to enhance the regenerative mechanisms. The neurogenic differentiation on CMT scaffolds was almost similar to the freshly prepared meningeal scaffolds and mimics with the natural nervous tissue developmental mechanisms which offer intact 3D-microarchitecture and hospitable microenvironment enriched with several crucial neurotrophins for long-term cell survival and function. Functional assessment of developed BHNC showed highly increased positive staining for pre-synaptic granules of Synapsis-1 along with MAP-2 antibody with punctuate distribution in axonal regions of the neuronal cells which was well supported by the gene expression analysis of functional transcripts. Given the significant improvement in the field may enable to generate more such ready to use functional BHNC for wider applicability in SCI repair/regeneration.
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http://dx.doi.org/10.1016/j.msec.2019.04.028DOI Listing
September 2019

Intraperitoneal transplantation of bioengineered humanized liver grafts supports failing liver in acute condition.

Mater Sci Eng C Mater Biol Appl 2019 May 14;98:861-873. Epub 2019 Jan 14.

Central Laboratory for Stem Cell Research and Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad 500058, Telangana, India; Dr. Habeebullah Life Sciences, Attapur, Hyderabad 500048, Telangana, India. Electronic address:

Acute liver failure (ALF) is one of the most devastating fatal conditions which have posed crucial challenges to the clinicians and researchers for identifying permanent cure. Currently liver transplantation has been considered as the only managerial option. However it's wider applicability has been limited owing to non-availability of quality donor organs, cost-intensiveness, surgical hitches, life-long use of immunosuppressive drugs and long-term complications. Since last decades, several liver support systems have been developed for the management of failing liver in acute condition. However, the major limitation has been the lack of natural biological support and long-term survival of the grafts post-transplantation. Repopulation of decellularized xenogeneic organs is one of the emerging technologies for development of humanized neo-organs for demanding regenerative application. However, the earlier reported studies do not fulfil the insistence to provide immunologically tolerable humanized liver grafts for clinical applications. Here we demonstrate an efficient approach to generate transplantable humanized liver grafts which provides long-term support to the failing liver in Acute Liver Failure (ALF) animal models. These bioengineered humanized liver tissue grafts expresses several liver specific transcripts and performed crucial synthetic (albumin production) and detoxification (urea synthesis) functions at comparative level to normal liver. Intraperitoneal transplantation of these humanized liver grafts offered favourable microenvironment to exchange toxic substances across the barrier during ALF condition and provided long-term survival and function of the graft. In summary, the results of present study provide a first proof of concept in pre-clinical ALF animal model for the applicability of these bioengineered humanized livers in the management of failing liver on demand and may be considered as potential bridge to liver transplantation.
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http://dx.doi.org/10.1016/j.msec.2019.01.045DOI Listing
May 2019

Activation of integrated stress response pathway regulates IL-1β production through posttranscriptional and translational reprogramming in macrophages.

Eur J Immunol 2019 02 4;49(2):277-289. Epub 2019 Jan 4.

Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, India.

Immune cells sense and programme its cellular machinery appropriately to the environmental changes through the activation of cytoprotective adaptive pathway so-called the "integrated stress response (ISR)". However, the mechanisms implicated in ISR-induced protective responses are poorly understood. Here, we show that ISR activation by arsenite (Ar) results in suppression of IL-1β production in macrophages and inhibition of DSS-induced colitis in a murine model through a novel posttranscriptional and translation regulatory (PTR) mechanism. Ar triggers PTR events through eIF2α-phosphorylation, which results in the attenuation of active polysome formation leading to the accumulation of translationally stalled IL-1β mRNAs. Translationally stalled IL-1β mRNAs recruit RNA-binding proteins (TIA-1/TIAR), resulting in the formation of RBP-RNA complexes known as stress granules (SGs). The SGs bound IL-1β mRNAs might undergo degradation through induction of autophagy. Also, we show that Ar posttranslationally impairs processing and secretion of IL-1β by diminishing inflammasome activation. Altogether, this study unveils a novel mechanism of IL-1β regulation and further suggests that pharmacological activation of cytoprotective ISR pathway might provide an effective therapeutic intervention against inflammatory diseases.
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http://dx.doi.org/10.1002/eji.201847513DOI Listing
February 2019

Bioengineered functional humanized livers: An emerging supportive modality to bridge the gap of organ transplantation for management of end-stage liver diseases.

World J Hepatol 2018 Nov;10(11):822-836

Central Laboratory for Stem Cell Research and Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad 500058, Telangana, India.

End stage liver diseases (ESLD) represent a major, neglected global public health crisis which requires an urgent action towards finding a proper cure. Orthotropic liver transplantation has been the only definitive treatment modality for ESLD. However, shortage of donor organs, timely unavailability, post-surgery related complications and financial burden on the patients limits the number of patients receiving the transplants. Since last two decades cell-based therapies have revolutionized the field of organ/tissue regeneration. However providing an alternative organ source to address the donor liver shortage still poses potential challenges. The developments made in this direction provide useful futuristic approaches, which could be translated into pre-clinical and clinical settings targeting appropriate applications in specific disease conditions. Earlier studies have demonstrated the applicability of this particular approach to generate functional organ in rodent system by connecting them with portal and hepatic circulatory networks. However, such strategy requires very high level of surgical expertise and also poses the technical and financial questions towards its future applicability. Hence, alternative sites for generating secondary organs are being tested in several types of disease conditions. Among different sites, omentum has been proved to be more appropriate site for implanting several kinds of functional tissue constructs without eliciting much immunological response. Hence, omentum may be considered as better site for transplanting humanized bioengineered generated livers, thereby creating a secondary organ at intra-omental site. However, the expertise for generating such bioengineered organs are limited and only very few centres are involved for investigating the potential use of such implants in clinical practice due to gap between the clinical transplant surgeons and basic scientists working on the concept evolution. Herein we discuss the recent advances and challenges to create functional secondary organs through intra-omental transplantation of generated bioengineered humanized livers and their further application in the management of ESLD as a supportive bridge for organ transplantation.
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http://dx.doi.org/10.4254/wjh.v10.i11.822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280164PMC
November 2018

Bioengineering Human Neurological Constructs Using Decellularized Meningeal Scaffolds for Application in Spinal Cord Injury.

Front Bioeng Biotechnol 2018 1;6:150. Epub 2018 Nov 1.

Central Laboratory for Stem Cell Research and Translational Medicine, CLRD, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, India.

Spinal cord injury (SCI) is one of the most devastating conditions echoes with inflammation, enhanced fibrosis and larger axonal gaps due to destruction of neurological cells which has caused continuous increasing mortality rate of SCI patients due to absence of suitable treatment modalities. The restoration of structural and functional aspect of damaged neurological tissues at the lesion site in spinal cord has been challenging. Recent developments have showed tremendous potential of neural stem cell-based strategies to form a neuronal relay circuit across the injury gap which facilitates some levels of improvement in SCI condition. However, to provide better therapeutic responses, critical mass of grafted cells must survive for long-term and differentiate into neuronal cells with well-developed axonal networks. Hence, development of tissue specific biological neuronal constructs is highly desirable to provide mechanical and biological support for long-term survival and function of neurological cells within natural biological niche. In this study, we report development of a tissue specific neuronal constructs by culturing human neural precursor cells on decellularized meningeal scaffolds to provide suitable biological neuronal construct which can be used to support mechanical, structural and functional aspect of damaged spinal cord tissues. This particular tissue specific biological construct is immunologically tolerable and provides precisely orchestral three-dimensional platform to choreograph the long-distance axonal guidance and more organized neuronal cell growth. It passes sufficient mechanical and biological properties enriched with several crucial neurotrophins required for long-term survival and function of neurological cells which is required to form proper axonal bridge to regenerate the damaged axonal connectomes at lesion-site in SCI.
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http://dx.doi.org/10.3389/fbioe.2018.00150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221909PMC
November 2018

Transcriptome meta-analysis identifies immune signature comprising of RNA binding proteins in ulcerative colitis patients.

Cell Immunol 2018 12 21;334:42-48. Epub 2018 Sep 21.

Central Laboratory for Stem Cell Research and Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad-500058, Telangana, India. Electronic address:

Ulcerative colitis (UC) is a persistent inflammatory illness, which is clinically categorised as Inflammatory bowel disease (IBD), affecting millions of people worldwide. The precise cause behind the pathology of the disease remains unknown. However, the involvement of multiple factors including genetic predisposition, immunological deregulations, microbiota imbalance, and environmental triggers has been suggested. Amongst all these factors, the over-active immunological response reported in UC patients seems to be a promising target for therapy. Moreover, identification of gene signatures associated with disease onset and progression would help in better understanding of the molecular mechanisms involved in the disease pathogenesis. Here, we have conducted meta-analysis of gene expression profiles of UC patient microarray datasets accessible in public databases and further validated the in-silico findings in UC patients' blood samples. Our study reveals that UC pathogenesis perturbs expression of several inflammatory genes. In addition, we report a novel gene signature comprising of TIA1 (T cell restricted intracellular antigen) and TIAR (TIA1 related protein; also known as TIAL1), which were found to be significantly downregulated in UC patients. TIA1 and TIAR are RNA-binding proteins (RBPs), which function as a translational represser by binding to ARE sequences in the 3' UTR of mRNAs encoding inflammatory mediators including cytokines. Our findings demonstrate that deletion of TIAR using gene specific siRNAs in-vitro results in enhanced production of inflammatory cytokine IL-1β. In conclusion, the findings of this study reveal that down regulation of TIA1/TIAR genes could be responsible for UC associated inflammation. This study highlights the usefulness of the meta-analysis approach in the identification of unique gene signatures that might deliver mechanistic insights into UC pathogenesis and possibly assist in discovery of prognostic markers and therapeutic interventions.
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http://dx.doi.org/10.1016/j.cellimm.2018.09.003DOI Listing
December 2018

Human-modified biogeographic patterns and conservation in game birds: The dilemma of the black francolin (Francolinus francolinus, Phasianidae) in Pakistan.

PLoS One 2018 5;13(10):e0205059. Epub 2018 Oct 5.

Department of Biology, University of Pisa, Pisa, Italy.

The ever-increasing human-mediated wildlife reshuffling is raising concern for the conservation of biodiversity. The loss of biological distinctiveness among regions lessens the genetic diversity and consequently the evolutionary potential of local biotas to tackle present-day global change and human disturbance. This process may be sometimes cryptic unless investigated by means of a molecular approach. In this respect, game birds are a paradigmatic case. The black francolin (Francolinus francolinus, Phasianidae) is a medium-sized galliform whose distribution range stretches from Cyprus to the Gulf of Bengal. Six morphologic subspecies are known, with three of which occurring in Pakistan, where the species is heavily hunted and used as pet for chirping competitions. We genotyped 98 samples (feathers) at both the entire mitochondrial DNA Control Region gene and nine microsatellite loci to get a deeper insight into the genetic diversity of the black francolin in Pakistan in order to offer cogent recommendations for its conservation management. We identified several mtDNA lineages that were consistent with the currently described subspecies/taxonomy whose pattern of co-occurrence is compatible with the geological history and the faunal movement routes of the region under study. However, the biparentally inherited microsatellites returned a quite discordant picture of an extensive, sex-biased genetic mixing due to the intensive relocations of already overharvested male individuals for chirping competitions. Our results indicated that the genetic integrity of the black francolin in Pakistan could be seriously at risk and call for monitoring and limiting its trade other than enhancing the public awareness of the importance of local biodiversity resources.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205059PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173408PMC
March 2019

Molecular dynamics of pancreatic transcription factors in bioengineered humanized insulin producing neoorgan.

Gene 2018 Oct 3;675:165-175. Epub 2018 Jul 3.

Central Laboratory for Stem Cell Research & Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad 500058, Telangana, India; Dr. Habeebullah Life Sciences, Attapur, Hyderabad 500030, Telangana, India. Electronic address:

Background: The present study has been aimed to identify molecular dynamics of pancreatic transcription factors (pTFs) during events of directed trans-differentiation of human hepatic progenitor cells (hHPCs) into insulin producing cells (InPCs) within bioengineered humanized neoorgan. The study demonstrates applicability of acellularized whole splenic scaffold (ASOS) to generate insulin producing humanized transplantable neoorgan through activation of pancreatic transcription factors.

Methods: An efficient acellularization process was developed for xenogeneic rat spleen using change in different gradients of reagents perfusion through splenic artery for varying time points. The acellularized xenogeneic spleen scaffold was characterized thoroughly for preservation of extra-cellular matrix and retention of organ specific vasculature and mechanical properties. Further scaffolds were sterilized and repopulated with hHPCs which were triggered using a stage wise induction with growth factors and hyperglycemic challenge for trans-differentiation into InPCs. Dynamics of pTFs alone or simultaneously during induction process was identified using gene expression analysis and immunological staining.

Results: The cells within the engineered neoorgan respond to growth factors and extrinsic hyperglycemic challenge and generate large number of InPCs under controlled dynamic regulation of pTFs. Highly controlled regulation of pTFs generates higher percentage of Nkx-6.1+/C-peptide+ cells within the engineered splenic scaffolds. Generation of high percentage of insulin and C-peptide positive cells in three-dimensional organ architecture responded better to hyperglycemic stimuli and produced higher quantity of insulin than 2D-culture system.

Conclusion: The present study provides a novel platform for designing effective regenerative strategies using whole organ scaffolds to control hyperglycemia under tight regulation of pTFs using humanized neoorgan system.
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http://dx.doi.org/10.1016/j.gene.2018.07.006DOI Listing
October 2018

Protective Role of Hypothermia Against Heat Stress in Differentiated and Undifferentiated Human Neural Precursor Cells: A Differential Approach for the Treatment of Traumatic Brain Injury.

Basic Clin Neurosci 2017 Nov-Dec;8(6):453-466

Central Laboratory for Stem Cell Research and Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Hyderabad, India.

Introduction: The present study aimed to explore protective mechanisms of hypothermia against mild cold and heat stress on highly proliferative homogeneous human Neural Precursor Cells (NPCs) derived from Subventricular Zone (SVZ) of human fetal brain.

Methods: CD133+ve enriched undifferentiated and differentiated human NPCs were exposed to heat stress at 42°C. Then, Western-blot quantification was performed using Hsp-70 (70 kilodalton heat shock proteins) recombinant protein. Finally, changes in pluripotency and Hsp-70 expression were measured using immunofluorescence staining and RT-qPCR (Quantitative reverse transcription PCR) analysis, respectively.

Results: Heat stress resulted in abnormal neurospheres development. The apoptosis rate was enhanced during long-term in vitro culture of neurospheres. Neurogenic differentiation reduced and showed aberrent phenotypes during heat stress. After hypothermia treatment significant improvement in neurospheres and neuronal cell morphology was observed.

Conclusion: Mild-hypothermia treatment induces attenuated heat shock response against heat stress resulting in induced HSP-70 expression that significantly improves structure and function of both undifferentiated human NPCs and differentiated neurons.
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http://dx.doi.org/10.29252/NIRP.BCN.8.6.453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010658PMC
June 2018

In vitro hemocompatability evaluation of gold nanoparticles capped with Lactobacillus plantarum derived lipase1.

Clin Hemorheol Microcirc 2018 ;69(1-2):197-205

Department of Biological Sciences, BITS Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, Hyderabad, Telangana, India.

Background: Gold nanoparticles (GNPs) are key diagnostic and therapeutic agents in biomedical sciences. Several studies have been carried out in different therapeutic areas such as in cancer treatment, antibacterial topical agents, imaging agents etc. There is a necessity to evaluate the gold nanoparticles cytotoxicity at all fronts. Since blood is the first point of contact in any therapy, it is required to have a thorough in vitro investigation of gold nanoparticles to avoid any adverse effects.

Objective: The objective of the current study is to evaluate the effect of gold nanoparticles capped with lipase on blood clotting factors, platelets, coagulation time and blood clotting strength.

Methods: Whole blood samples were drawn from healthy volunteers. Plasma and plasma with platelets were isolated from the blood and all the samples were treated with lipase capped gold nanoparticles, except control. Plasma fibrinogen formed in the blood coagulation process after contacting with nanoparticles was quantitatively evaluated. In addition, platelet aggregation, blood clotting kinetics, strength of the blood clot and time were evaluated post nanoparticle treatment.

Results: The work primarily explores the effect of GNPs on blood with changing concentrations of lipase capping. Plasma fibrinogen levels of plasma samples were found to be moderately elevated, however, there is no significant effect on blood clotting kinetics, strength, and platelet aggregation. Also, the study showed that lipase capped GNPs did not result in aggregation upon interaction with plasma components and remained stable for 1 hour after incubation.

Conclusions: Our study revealed that lipase capped GNPs synthesized using NaBH4 approach were stable and hemocompatible. There is an increase in fibrinogen levels after the exposure to nanoparticles, an observation which is consistent with other studies. However, the functional consequences of such increase are unknown. The results of no significant platelet aggregation, change in blood clotting time, kinetics, and clot strength revealed the non-toxic effect of lipase capped GNPs towards blood components, which is essential for any in vivo applications.
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http://dx.doi.org/10.3233/CH-189117DOI Listing
June 2018

Role of drug transporters and heat shock proteins during ethanol exposure to human neural precursor cells and its lineages.

Tissue Cell 2018 Apr 7;51:14-23. Epub 2018 Feb 7.

Central Laboratory for Stem Cell Research & Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, 500058, Telangana, India. Electronic address:

Introduction: Ethanol exposure to developing brain may alter the growth and differentiation of neurological cells resulting in unfavorable pathologies. Earlier studies have provided very limited mechanistic insights of cellular and molecular mechanisms which do not mimic with human situation due to varying cell types and poses potential challenges for investigation. Therefore, the present study was undertaken to evaluate the role of ABC transporters and heat shock proteins mediated response in human neural precursor cells (NPCs) and its lineages during proliferation and lineage differentiation against ethanol exposure.

Methods: Effect of ethanol exposure was examined for neuronal cell survival and variation in cellular phenotype during neurospheres development and lineage differentiation. Generation of reactive oxygen species, and variation in cell cycle was identified along with transcriptional profiling for pluripotent markers (Nestin, NCAM, Sox-2, and Notch-2), drug transporters (ABCB1 and ABCG2) and stress protein (HSP70) during ethanol exposure.

Results: ABC transporters as well as HSP70 mRNA expression was higher during proliferation as compared to differentiation with chronic ethanol (1 M) exposure (p < 0.01). Ethanol exposure resulted in higher variability in size and shape of developing neurospheres and decreased ability to form new neurosphere colonies. Significant changes were observed in dendrite development due to late ethanol exposure (p < 0.0001).

Conclusion: The present study demonstrated significant role of ABC transporters and HSP70 proteins in providing defense against ethanol-induced damage in human neurological cells. However, the over-expression of ABC transporter and HSP-70 proteins during such pathological conditions do not provide complete defense and additional strategies are required to repair the damage.
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http://dx.doi.org/10.1016/j.tice.2018.02.001DOI Listing
April 2018

Amino acid starvation sensing dampens IL-1β production by activating riboclustering and autophagy.

PLoS Biol 2018 04 5;16(4):e2005317. Epub 2018 Apr 5.

Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India.

Activation of the amino acid starvation response (AAR) increases lifespan and acute stress resistance as well as regulates inflammation. However, the underlying mechanisms remain unclear. Here, we show that activation of AAR pharmacologically by Halofuginone (HF) significantly inhibits production of the proinflammatory cytokine interleukin 1β (IL-1β) and provides protection from intestinal inflammation in mice. HF inhibits IL-1β through general control nonderepressible 2 kinase (GCN2)-dependent activation of the cytoprotective integrated stress response (ISR) pathway, resulting in rerouting of IL-1β mRNA from translationally active polysomes to inactive ribocluster complexes-such as stress granules (SGs)-via recruitment of RNA-binding proteins (RBPs) T cell-restricted intracellular antigen-1(TIA-1)/TIA-1-related (TIAR), which are further cleared through induction of autophagy. GCN2 ablation resulted in reduced autophagy and SG formation, which is inversely correlated with IL-1β production. Furthermore, HF diminishes inflammasome activation through suppression of reactive oxygen species (ROS) production. Our study unveils a novel mechanism by which IL-1β is regulated by AAR and further suggests that administration of HF might offer an effective therapeutic intervention against inflammatory diseases.
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http://dx.doi.org/10.1371/journal.pbio.2005317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903674PMC
April 2018

Bioengineered humanized livers as better three-dimensional drug testing model system.

World J Hepatol 2018 Jan;10(1):22-33

Central Laboratory for Stem Cell Research and Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Hyderabad 500058, Telangana, India.

Aim: To develop appropriate humanized three-dimensional model system for drug testing.

Methods: Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the acellularized liver scaffolds which mimics with the natural organ anatomy and physiology. Six cytochrome P-450 probes were used to enable efficient identification of drug metabolism in bioengineered humanized livers. The drug metabolism study in bioengineered livers was evaluated to identify the absorption, distribution, metabolism, excretion and toxicity responses.

Results: The bioengineered humanized livers showed cellular and molecular characteristics of human livers. The bioengineered liver showed three-dimensional natural architecture with intact vasculature and extra-cellular matrix. Human hepatic cells were engrafted similar to the human liver. Drug metabolism studies provided a suitable platform alternative to available and models for identifying cellular and molecular dynamics of pharmacological drugs.

Conclusion: The present study paves a way towards the development of suitable humanized preclinical model systems for pharmacological testing. This approach may reduce the cost and time duration of preclinical drug testing and further overcomes on the anatomical and physiological variations in xenogeneic systems.
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http://dx.doi.org/10.4254/wjh.v10.i1.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787681PMC
January 2018

Enhanced neuroprotective effect of mild-hypothermia with VPA against ethanol-mediated neuronal injury.

Tissue Cell 2017 Dec 14;49(6):638-647. Epub 2017 Sep 14.

Central Laboratory for Stem Cell Research and Translational Medicine, CLRD, Deccan College of Medical Sciences, Hyderabad 500058, Telangana, India. Electronic address:

Introduction: Progress in understanding pathophysiological mechanisms and the development of targeted regenerative strategies have been hampered by the lack of predictive disease models, specifically for the conditions to which affected cell types are inaccessible. The present study has aimed to unearth the role of valproic acid (VPA) and mild hypothermia (MH) as promising strategy to enhance the neuroprotective mechanisms in undifferentiated and differentiated human neural precursor cells (hNPCs) against ethanol-induced damage.

Methods: 5mM VPA alone or in combination with MH (33°C) was used to prevent the damage in proliferating and differentiating hNPCs. CD133+ve enriched hNPCs were cultured in vitro and exposed to 1M chronic ethanol concentration for 72h and followed by VPA and MH treatment for 24h. Morphometric analysis was performed to identify changes in neurospheres development and neuronal cell phenotypes. Flow cytometry and RT-qPCR analysis was performed to investigate alterations in key molecular pathways involved in cell survival and signaling.

Results: Combination of VPA with MH displayed higher proportion of neuronal cell viability as compared to single treatment. Combination treatment was most effective in reducing apoptosis and reactive oxygen species levels in both the undifferentiated and differentiated hNPCs. VPA with MH significantly improved neuronal cell phenotype, active chromatin modeling, chaperon and multi-drug resistant pumps activity and expression of neuronal signaling molecules.

Conclusion: The study provided an efficient and disease specific in vitro model and demonstrated that combined treatment with VPA and MH activates several neuroprotective mechanisms and provides enhanced protection against ethanol-induced damage in cultured undifferentiated and differentiated hNPCs.
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http://dx.doi.org/10.1016/j.tice.2017.09.004DOI Listing
December 2017

Use of Biocompatible Sorafenib-gold Nanoconjugates for Reversal of Drug Resistance in Human Hepatoblatoma Cells.

Sci Rep 2017 08 17;7(1):8539. Epub 2017 Aug 17.

Clinical Research Facility, Medical Biotechnology Complex, CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Habsiguda, Hyderabad, 500007, Telangana, India.

The present study identifies the potential of highly biocompatible SF-GNP nano-conjugate to enhance the chemotherapeutic response to combat drug resistance in cancer cells. We developed a stable colloidal suspension of sorafenib-gold nanoconjugate (SF-GNP) of <10 nm size in aqueous medium for reverting the cancer drug resistance in SF-resistant HepG2 cells in a 3D ex-vivo model system. In-vivo biocompatibility assay of SF-GNPs showed absence of systemic toxicological effects including hematological, biochemical and histological parameters. More importantly, the histopathological analysis of vital organs such as liver, brain, lung, kidney and heart showed very least or no sign of inflammation, cell infiltration, necrosis, tissue disorganization or fibrotic reactions after intra-peritoneal administration of SF-GNP nanoconjugates in animals. However, SF-GNP nanoconjugates significantly reduced (>80%) the percentage cell survival and the size and number of SF resistant solid tumor colonies of HepG2 cells in 3D model system. The exposure of SF-GNP nanoconjugate to SF resistant HepG2 cell colonies also provided evidence for anti-proliferative effect and reversal of drug resistance by elucidating the molecular regulatory mechanisms of extracellular matrix factor (CD147), tumor growth factor (TGF-β), hepatoma upregulated protein (hURP) and drug transporter (ABCG-2).
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http://dx.doi.org/10.1038/s41598-017-08878-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561190PMC
August 2017

A Comprehensive Gene Expression Meta-analysis Identifies Novel Immune Signatures in Rheumatoid Arthritis Patients.

Front Immunol 2017 2;8:74. Epub 2017 Feb 2.

Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad , Hyderabad , India.

Rheumatoid arthritis (RA), a symmetric polyarticular arthritis, has long been feared as one of the most disabling forms of arthritis. Identification of gene signatures associated with RA onset and progression would lead toward development of novel diagnostics and therapeutic interventions. This study was undertaken to identify unique gene signatures of RA patients through large-scale meta-profiling of a diverse collection of gene expression data sets. We carried out a meta-analysis of 8 publicly available RA patients' (107 RA patients and 76 healthy controls) gene expression data sets and further validated a few meta-signatures in RA patients through quantitative real-time PCR (RT-qPCR). We identified a robust meta-profile comprising 33 differentially expressed genes, which were consistently and significantly expressed across all the data sets. Our meta-analysis unearthed upregulation of a few novel gene signatures including , and , which were validated in peripheral blood mononuclear cell samples of RA patients. Further, functional and pathway enrichment analysis reveals perturbation of several meta-genes involved in signaling pathways pertaining to inflammation, antigen presentation, hypoxia, and apoptosis during RA. Additionally, PLCG2 (phospholipase Cγ2) popped out as a novel meta-gene involved in most of the pathways relevant to RA including inflammasome activation, platelet aggregation, and activation, thereby suggesting PLCG2 as a potential therapeutic target for controlling excessive inflammation during RA. In conclusion, these findings highlight the utility of meta-analysis approach in identifying novel gene signatures that might provide mechanistic insights into disease onset, progression and possibly lead toward the development of better diagnostic and therapeutic interventions against RA.
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http://dx.doi.org/10.3389/fimmu.2017.00074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288395PMC
February 2017

Hepatic stem cells: A viable approach for the treatment of liver cirrhosis.

World J Stem Cells 2015 Jun;7(5):859-65

Md Aejaz Habeeb, Sandeep Kumar Vishwakarma, Avinash Bardia, Aleem Ahmed Khan, Center for Liver Research and Diagnostics, Deccan College of Medical Sciences, Hyderabad 500058, Andhra Pradesh, India.

Liver cirrhosis is characterized by distortion of liver architecture, necrosis of hepatocytes and regenerative nodules formation leading to cirrhosis. Various types of cell sources have been used for the management and treatment of decompensated liver cirrhosis. Knowledge of stem cells has offered a new dimension for regenerative therapy and has been considered as one of the potential adjuvant treatment modality in patients with end stage liver diseases (ESLD). Human fetal hepatic progenitor cells are less immunogenic than adult ones. They are highly propagative and challenging to cryopreservation. In our earlier studies we have demonstrated that fetuses at 10-18 wk of gestation age contain a large number of actively dividing hepatic stem and progenitor cells which possess bi-potent nature having potential to differentiate into bile duct cells and mature hepatocytes. Hepatic stem cell therapy for the treatment of ESLD is in their early stage of the translation. The emerging technology of decellularization and recellularization might offer a significant platform for developing bioengineered personalized livers to come over the scarcity of desired number of donor organs for the treatment of ESLD. Despite these significant advancements long-term tracking of stem cells in human is the most important subject nowadays in order to answer several unsettles issues regarding the route of delivery, the choice of stem cell type(s), the cell number and the time-point of cell delivery for the treatment in a chronic setting. Answering to these questions will further contribute to the development of safer, noninvasive, and repeatable imaging modalities that could discover better cell therapeutic approaches from bench to bed-side. Combinatorial approach of decellularization and nanotechnology could pave a way towards the better understanding in determination of cell fate post-transplantation.
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http://dx.doi.org/10.4252/wjsc.v7.i5.859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478632PMC
June 2015

Magnetic nanoparticle tagged stem cell transplantation in spinal cord injury: A promising approach for targeted homing of cells at the lesion site.

Neurol India 2015 May-Jun;63(3):460-1

Centre for Liver Research and Diagnostics, Central Laboratory for Stem Cell Research and Translational Medicine, Deccan College of Medical Sciences, Kanchanbagh; Centre for Cellular and Molecular Medicine, Salar E Millat Sultan Salahuddin Owaisi Research Centre, PEH, Shahalibada, Hyderabad, Telangana, India.

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http://dx.doi.org/10.4103/0028-3886.158294DOI Listing
June 2015

Repopulation of decellularized whole organ scaffold using stem cells: an emerging technology for the development of neo-organ.

J Artif Organs 2014 Dec 17;17(4):291-300. Epub 2014 Jul 17.

Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, 500 058, Andhra Pradesh, India,

Demand of donor organs for transplantation in treatment of organ failure is increasing. Hence there is a need to develop new strategies for the alternative sources of organ development. Attempts are being made to use xenogenic organs by genetic manipulation but the organ rejection against human always has been a major challenge for the survival of the graft. Advancement in the genetic bioengineering and combination of different allied sciences for the development of humanized organ system, the therapeutic influence of stem cell fraction on the reconstitution of organ architecture and their regenerative abilities in different tissues and organs provides a better approach to solve the problem of organ shortage. However, the available strategies for generating the organ/tissue scaffolds limit its application due to the absence of complete three-dimensional (3D) organ architecture, mechanical strength, long-term cell survival, and vascularization. Repopulation of whole decellularized organ scaffolds using stem cells has added a new dimension for creating new bioengineered organs. In recent years, several studies have demonstrated the potential application of decellularization and recellularization approach for the development of functional bio-artificial organs. With the help of established procedures for conditioning, extensive stem cells and organ engineering experiments/transplants for the development of humanized organs will allow its preclinical evaluation for organ regeneration before translation to the clinic. This review focuses on the major aspects of organ scaffold generation and repopulation of different types of whole decellularized organ scaffolds using stem cells for the functional benefit and their confines.
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http://dx.doi.org/10.1007/s10047-014-0780-2DOI Listing
December 2014

Multilocus phylogeny of the avian family Alaudidae (larks) reveals complex morphological evolution, non-monophyletic genera and hidden species diversity.

Mol Phylogenet Evol 2013 Dec 21;69(3):1043-56. Epub 2013 Jun 21.

Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, PR China; Swedish Species Information Centre, Swedish University of Agricultural Sciences, Box 7007, SE-750 07 Uppsala, Sweden; Percy FitzPatrick Institute of African Ornithology, DST/NRF Centre of Excellence, University of Cape Town, Rondebosch 7700, South Africa. Electronic address:

The Alaudidae (larks) is a large family of songbirds in the superfamily Sylvioidea. Larks are cosmopolitan, although species-level diversity is by far largest in Africa, followed by Eurasia, whereas Australasia and the New World have only one species each. The present study is the first comprehensive phylogeny of the Alaudidae. It includes 83.5% of all species and representatives from all recognised genera, and was based on two mitochondrial and three nuclear loci (in total 6.4 kbp, although not all loci were available for all species). In addition, a larger sample, comprising several subspecies of some polytypic species was analysed for one of the mitochondrial loci. There was generally good agreement in trees inferred from different loci, although some strongly supported incongruences were noted. The tree based on the concatenated multilocus data was overall well resolved and well supported by the data. We stress the importance of performing single gene as well as combined data analyses, as the latter may obscure significant incongruence behind strong nodal support values. The multilocus tree revealed many unpredicted relationships, including some non-monophyletic genera (Calandrella, Mirafra, Melanocorypha, Spizocorys). The tree based on the extended mitochondrial data set revealed several unexpected deep divergences between taxa presently treated as conspecific (e.g. within Ammomanes cinctura, Ammomanes deserti, Calandrella brachydactyla, Eremophila alpestris), as well as some shallow splits between currently recognised species (e.g. Certhilauda brevirostris-C. semitorquata-C. curvirostris; Calendulauda barlowi-C. erythrochlamys; Mirafra cantillans-M. javanica). Based on our results, we propose a revised generic classification, and comment on some species limits. We also comment on the extraordinary morphological adaptability in larks, which has resulted in numerous examples of parallel evolution (e.g. in Melanocorypha mongolica and Alauda leucoptera [both usually placed in Melanocorypha]; Ammomanopsis grayi and Ammomanes cinctura/deserti [former traditionally placed in Ammomanes]; Chersophilus duponti and Certhilauda spp.; Eremopterix hova [usually placed in Mirafra] and several Mirafra spp.), as well as both highly conserved plumages (e.g. within Mirafra) and strongly divergent lineages (e.g. Eremopterix hova vs. other Eremopterix spp.; Calandrella cinerea complex vs. Eremophila spp.; Eremalauda dunni vs. Chersophilus duponti; Melanocorypha mongolica and male M. yeltoniensis vs. other Melanocorypha spp. and female M. yeltoniensis). Sexual plumage dimorphism has evolved multiple times. Few groups of birds show the same level of disagreement between taxonomy based on morphology and phylogenetic relationships as inferred from DNA sequences.
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http://dx.doi.org/10.1016/j.ympev.2013.06.005DOI Listing
December 2013

New insights into the intricate taxonomy and phylogeny of the Sylvia curruca complex.

Mol Phylogenet Evol 2013 Apr 12;67(1):72-85. Epub 2013 Jan 12.

Section of Systematics and Biodiversity, Biology and Environmental Sciences, University of Gothenburg, Box 463, SE-405 30 Gothenburg, Sweden.

We use the mitochondrial cytochrome b from 213 individuals and the three nuclear introns BRM 15, myoglobin 2 and ODC 6-7 from a smaller subsample to evaluate the taxonomy of the Lesser Whitethroat Sylvia curruca (Aves, Passeriformes, Sylviidae) complex, which has long been controversial. We sequenced type material of the taxa althaea, blythi, margelanica and minula, and used topotypical material of caucasica, chuancheica, curruca and telengitica. The nuclear introns fail to resolve the complex, but cytochrome b recovers six major clades, revealing genetically identifiable populations corresponding to previously named taxa, and we propose that the names althaea, blythi, curruca, halimodendri, margelanica and minula, respectively, should be used for these. The margelanica clade is suggested to have a more extensive distribution than previously known, including both the taxon telengitica and a population in eastern Mongolia. The taxon minula is found to have a more restricted range than generally believed, only breeding in China. According to the mitochondrial gene tree, there is a basal dichotomy, with the taxa althaea, blythi, halimodendri and margelanica being part of one clade, well separated from a clade containing curruca and minula. Dating analysis suggests that a basal divergence separating curruca and minula from the other four taxa occurred between 4.2 and 7.2 mya; these two then diverged between 2.3 and 4.4 mya. The splits between the althaea, blythi, halimodendri and margelanica lineages is inferred to have occurred later, approximately between 1.0 and 2.5 mya (all 95% HPD). The nucleotide data suggest significant departure from demographic equilibrium in blythi (clade 1a), halimodendri (clade 2a) and minula, whereas tendencies are weaker for other clades. We propose that the names althaea, blythi, curruca, halimodendri, margelanica and minula should be used for the major clades. However, whether these are treated as subspecies or species is largely a matter of species definition and is not resolved by our data.
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http://dx.doi.org/10.1016/j.ympev.2012.12.023DOI Listing
April 2013

Neural stem cells & supporting cells--the new therapeutic tools for the treatment of spinal cord injury.

Indian J Med Res 2009 Oct;130(4):379-91

Care Hospital, The Institute of Medical Sciences, Hyderabad, India.

Stem cells play important role in the development and in the maintenance of specific tissues. They have been identified in majority of the organs like liver, blood, skin and intestine. Role of stem cells in regenerative medicine have been implicated in many chronic diseases. Stem cell research is a new opportunity to those patients whose organs are damaged or diseased. The discovery of stem cells in central and peripheral nervous system is relatively recent. Spinal cord injury is one of the major neurological disaster affecting mostly young lives. Stem cell transplantation in spinal cord injury patients have shown encouraging results. Different sources of stem cells are being exploited for spinal cord injury as well as other neurological disorders.
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October 2009

Characterization of hepatic progenitors from human fetal liver during second trimester.

World J Gastroenterol 2008 Oct;14(37):5730-7

Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.

Aim: To enrich hepatic progenitors using epithelial cell adhesion molecule (EpCAM) as a marker from human fetal liver and investigate the expression of human leukocyte antigen (HLA) and their markers associated with hepatic progenitor cells.

Methods: EpCAM +ve cells were isolated using magnetic cell sorting (MACS) from human fetuses (n = 10) at 15-25 wk gestation. Expression of markers for hepatic progenitors such as albumin, alpha-fetoprotein (AFP), CD29 (integrin beta1), CD49f (integrin alpha6) and CD90 (Thy 1) was studied by using flow cytometry, immunocytochemistry and RT-PCR; HLA class I (A, B, C) and class II (DR) expression was studied by flow cytometry only.

Results: FACS analysis indicated that EpCAM +ve cells were positive for CD29, CD49f, CD90, CD34, HLA class I, albumin and AFP but negative for HLA class II (DR) and CD45. RT PCR showed that EpCAM +ve cells expressed liver epithelial markers (CK18), biliary specific marker (CK19) and hepatic markers (albumin, AFP). On immunocytochemical staining, EpCAM +ve cells were shown positive signals for CK18 and albumin.

Conclusion: Our study suggests that these EpCAM +ve cells can be used as hepatic progenitors for cell transplantation with a minimum risk of alloreactivity and these cells may serve as a potential source for enrichment of hepatic progenitor.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748210PMC
http://dx.doi.org/10.3748/wjg.14.5730DOI Listing
October 2008
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