Life Sciences Commons^™

Does Red Blood Cell Distribution Width (Rdw) Improve Evaluation Of Microcytic Anaemias?, Muhammad Sajjad Baqar, Mohammad Khurshid, A Molla

Mohammad Khurshid

Abstract The red cell distribution width (RDW) is an index of the variation in red cells size (anisocytosis). A study was conducted to examine the validity of using RDW in improving classification of microcytic anaemias. A total of 300 blood samples collected from a patient population aged 3 months to 55 years who were referred for haemoglobin electrophoresis were examined at The Aga Khan University Hospital (AKUH). On complete blood count, initially 200 patients (66.6%) were found to have hypochromic microcytic anaemia. Following haemoglobin electrophoresis 41% (821200) patients were diagnosed to have thalassemia minor and 59% (1181200) had hypochromic microcytic …

Chromosomal Abnormalities In Primary Myelodysplastic Syndrome, Anila Rashid, Mohammad Khurshid, Usman Shaikh, Salman Adil

Mohammad Khurshid

Objective: To determine the frequency of cytogenetic abnormalities in patients diagnosed as primary myelodysplastic syndrome (MDS) using conventional karyotyping. Study Design: Case series. Place and Duration of Study: The Clinical Laboratory, The Aga Khan University Hospital, Karachi, between January 2006 - June 2012. Methodology: Patients of all ages and either gender who fulfilled WHO criteria for MDS were included. Cytogenetic analysis was conducted at the time of diagnosis. Patients who had secondary MDS were excluded from analysis. Chromosome identification and karyotype description was done according to the International System for Chromosome Nomenclature (ISCN, 1995) and described as frequency percentage. Results: …

Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer

Celia A. Schiffer

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein …

Freshwater Fungal Infections, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Fungal infections as a result of freshwater exposure or trauma are fortunately rare. Etiologic agents are varied, but commonly include filamentous fungi and Candida. This narrative review describes various sources of potential freshwater fungal exposure and the diseases that may result, including fungal keratitis, acute otitis externa and tinea pedis, as well as rare deep soft tissue or bone infections and pulmonary or central nervous system infections following traumatic freshwater exposure during natural disasters or near-drowning episodes. Fungal etiology should be suspected in appropriate scenarios when bacterial cultures or molecular tests are normal or when the infection worsens or fails …

Symptomatic Surgically Treated Non-Neoplastic Cysts Of The Central Nervous System: A Clinicopathological Study From Pakistan, Nasir Ud Din, Huma Arshad, Zubair Ahmad, Sheema H Hasan, Mohammad Ehsan Bar

Zubair Ahmad

Objective: To report clinicopathologic features of symptomatic surgically removed non-neoplastic cysts of the central nervous system (CNS). Study Design: Case series. Place and Duration of Study: The Aga Khan University Hospital, Karachi, from 2003 to 2012. Methodology: All non-neoplastic CNS cysts reported during the study period were retrieved and reviewed. Age, gender, location, histologic type and clinical features were noted. Results: A total of 124 cysts were diagnosed in the study period. These included 44 epidermoid cysts (mean age 30.5 ± 13.8 years), 35 colloid cysts (mean age 31 ± 13.2 years), 32 arachnoid cysts (mean age 24.8 ± 20.2 …

In-House Daily Consensus Conference: An Important Quality Control/Quality Assurance Activity--Experience At A Major Referral Center., Amna Khurshid, Zubair Ahmad, Asim Qureshi

Zubair Ahmad

Background:For every practicing histopathologist, improvement of diagnostic accuracy is an important objective. Personal consults are an important component of quality control (QC)/quality assurance (QA) in our Section of Histopathology. In addition, the College of American Pathologists recommends a daily in-house consensus conference, which is a prospective system by which all difficult and problematic cases are reviewed and discussed and signed out by consensus. Design: In-house consensus conference is held daily using a multi-headed microscope. This collegial session is run by the seniormost consultant in the section and is attended by all histopathology consultants and residents. The consultants and residents …

Histological Pattern Of Ovarian Neoplasma., Zubair Ahmad, Naila Kayani, Sheema H. Hasan, Suhail Muzaffar, Muhammad Shafiq Gill

Zubair Ahmad

Abstract Objective: To see the morphological pattern of benign and malignant ovarian neoplasms. Method: Retrospective study of all consecutive cases of ovarian neoplasms diagnosed at Aga Khan University Hospital between 1st January 1993 and 30th September 1998. Setting: The Section of Histopathology, AKUH, Karachi. Observation: Of 855 ovarian tumours 506 (59.18%) were benign and 349(40.81%) malignant. Surface epithelial - stromal tumours comprised 63.50% of all tumours. Benign cystic teratoma was the commonest benign tumour (35.17% of all benign tumours) and serous cystadenocarcinoma was the commonest malignant tumour (33.33% of all malignant tumours). Mucinous cystadenocarcinomas are more common in our population …

Frequency Of Hereditary Thrombophilia: An Akuh Experience., Safoorah Khalid, Raihan Sajid, Salman Adil, Mohammad Khurshid

Salman Naseem Adil

Abstract Objective: To determine the frequency of various causes of hereditary thrombophilia at a referral laboratory and the age and gender distribution. Methods: This is a descriptive study incorporating a retrospective analysis of requests for thrombophilia screening sent to Clinical laboratory, Aga Khan University Hospital from November 1995 to May 2002.Patients were screened for hereditary causes of thrombophilia including Protein C, Protein S, antithrombin III, Factor V Leiden and homocysteine. Frequency of each disorder; and age and sex distribution was determined. Results: All the patients suspected clinically for thrombophilia were screened. Of the 2825 patients, 70 were diagnosed to have …

Emergence Of Carbapenem Resistant Gram Negative And Vancomycin Resistant Gram Positive Organisms In Bacteremic Isolates Of Febrile Neutropenic Patients: A Descriptive Study., Seema Irfan, Faiza Idrees, Vikram Mehraj, Faizah Habib, Salman Adil, Rumina Hasan

Salman Naseem Adil

Background:This study was conducted to evaluate drug resistance amongst bacteremic isolates of febrile neutropenic Patients with particular emphasis on emergence of carbapenem resistant Gram negative bacteria and vancomycin resistant Enterococcus species. Methods: A descriptive study was performed by reviewing the blood culture reports from febrile neutropenic Patients during the two study periods i.e., 1999-00 and 2001-06. Blood cultures were performed using BACTEC 9240 automated system. Isolates were identified and antibiotic sensitivities were done using standard microbiological procedures. Results: Seven twenty six febrile neutropenic Patients were admitted during the study period. A total of 5840 blood cultures were received, off these …

Chromosomal Abnormalities In Primary Myelodysplastic Syndrome, Anila Rashid, Mohammad Khurshid, Usman Shaikh, Salman Adil

Salman Naseem Adil

Objective: To determine the frequency of cytogenetic abnormalities in patients diagnosed as primary myelodysplastic syndrome (MDS) using conventional karyotyping. Study Design: Case series. Place and Duration of Study: The Clinical Laboratory, The Aga Khan University Hospital, Karachi, between January 2006 - June 2012. Methodology: Patients of all ages and either gender who fulfilled WHO criteria for MDS were included. Cytogenetic analysis was conducted at the time of diagnosis. Patients who had secondary MDS were excluded from analysis. Chromosome identification and karyotype description was done according to the International System for Chromosome Nomenclature (ISCN, 1995) and described as frequency percentage. Results: …

Complete Genome Sequence Of Spiroplasma Citri Strain R8-A2 T , Causal Agent Of Stubborn Disease In Citrus Species, Robert E. Davis, Jonathan Shao, Yan Zhao, Gail E. Gasparich, Brady J. Gaynor, Nicole Donofrio

Gail Gasparich

In Vitro Studies On Metabolism Of Salvinorin A, Lukasz M. Kutrzeba, Vardan T. Karamyan, Robert C. Speth, John S. Williamson, Jordan K. Zjawiony

John S. Williamson

Microbial transformation of natural products is a well established model for mammalian metabolism. Salvinorin A, a diterpenoid isolated from the hallucinogenic mint Salvia divinorum Epling & Játiva-M (Lamiaceae), is a potent non-nitrogenous κ-opioid receptor agonist. The metabolism of salvinorin A has still not yet been well established. Thirty fungal species were screened for the ability to metabolize salvinorin A. We observed that salvinorin A undergoes fast hydrolysis of the acetate group at carbon atom C2, resulting in formation of the pharmacologically inactive product, salvinorin B. Ex vivo experiments were also performed using organelle fractions isolated from rat liver and brain. …

Flagellar Formation In C-Ring-Defective Mutants By Overproduction Of Flii, The Atpase Specific For Flagellar Type Iii Secretion, Manabu Konishi, Masaomi Kanbe, Jonathan L. Mcmurry, Shin-Ichi Aizawa

Jonathan McMurry

The flagellar cytoplasmic ring (C ring), which consists of three proteins, FliG, FliM, and FliN, is located on the cytoplasmic side of the flagellum. The C ring is a multifunctional structure necessary for flagellar protein secretion, torque generation, and switching of the rotational direction of the motor. The deletion of any one of the fliG, fliM, and fliN genes results in a Fla - phenotype. Here, we show that the overproduction of the flagellum-specific ATPase FliI overcomes the inability of basal bodies with partial C-ring structures to produce complete flagella. Flagella made upon FliI overproduction were paralyzed, indicating that an …

Environmental Implications Of Francisella Tularensis Biofilms, Jeffrey J. Margolis '00

Jeffrey Margolis

Francisella tularensis survives in one of the widest environmental ranges of any pathogen. Numerous mammals and arthropod vectors are infected by this highly virulent organism. How this zoonotic pathogen persists outside of its many hosts remains unexplored. We aimed to examine how F. tularensis interacts with environmental surfaces, and hypothesized that biofilm formation may enable survival of this organism in nature. By understanding the role these surface-attached bacterial communities play in F. tularensis ecology, we hope to gain insight into the mechanisms of environmental persistence and transmission of this pathogen.

We identify chitin as a potential non-host niche for F. …

Genomic Plasticity And Rapid Host Switching Can Promote The Evolution Of Generalism: A Case Study In The Zoonotic Pathogen Campylobacter, Dan J. Woodcock, Peter Krusche, Norval J. C. Strachan, Ken J. Forbes, Frederick M. Cohan, Guillaume Meric, Samuel K. Sheppard

Frederick M. Cohan

Toward The History Of Study Of Symbiogenesis: On The English Translation Of B. M. Kozo-Polyansky’S A New Principle Of Biology (1924), Victor Fet

Victor Fet

We reproduce the text by Victor Fet, which was read on 6 October 2011 at the Moscow Society of Naturalists during the presentation of new book translation (B.M. Kozo- Polyansky. Symbiogenesis: A New Principle of Evolution / transl. by Victor Fet; ed. by Victor Fet & Lynn Margulis. Cambridge, Mass.: Harvard University Press, 2010. 138 p.) This half- forgotten book by Boris M. Kozo-Polyansky was known only by name to Western biologists. Victor Fet gives a brief history of this new translation, enthusiastically initiated and supported by Lynn Margulis (1938–2011), a famous naturalist who was always eager to gave credit …

Jmh Dissertation 2016.Pdf, Jennifer Hayashi

Jennifer Hayashi

Overlap In The Seasonal Infection Patterns Of Avian Malaria Parasites And West Nile Virus In Vectors And Hosts, Matthew C. I. Medeiros, Robert E. Ricklefs, Jeffrey D. Brawn, Marilyn O. Ruiz, Tony L. Goldberg, Gabriel L. Hamer

Robert Ricklefs

Leishmania Amazonensis Engages Cd36 To Drive Parasitophorous Vacuole Maturation, Kendi Okuda, Mei Tong, Brian Dempsey, Kathryn J. Moore, Ricardo T. Gazzinelli, Neal S. Silverman

Neal Silverman

Leishmania amastigotes manipulate the activity of macrophages to favor their own success. However, very little is known about the role of innate recognition and signaling triggered by amastigotes in this host-parasite interaction. In this work we developed a new infection model in adult Drosophila to take advantage of its superior genetic resources to identify novel host factors limiting Leishmania amazonensis infection. The model is based on the capacity of macrophage-like cells, plasmatocytes, to phagocytose and control the proliferation of parasites injected into adult flies. Using this model, we screened a collection of RNAi-expressing flies for anti-Leishmania defense factors. Notably, we …

Type I Interferon Induction By Neisseria Gonorrhoeae: Dual Requirement Of Cyclic Gmp-Amp Synthase And Toll-Like Receptor 4, Warrison A. Andrade, Sarika Agarwal, Shunyan Mo, Scott A. Shaffer, Joseph P. Dillard, Tobias Schmidt, Veit Hornung, Katherine A. Fitzgerald, Evelyn A. Kurt-Jones, Douglas T. Golenbock

Katherine A. Fitzgerald

The innate immune system is the first line of defense against Neisseria gonorrhoeae (GC). Exposure of cells to GC lipooligosaccharides induces a strong immune response, leading to type I interferon (IFN) production via TLR4/MD-2. In addition to living freely in the extracellular space, GC can invade the cytoplasm to evade detection and elimination. Double-stranded DNA introduced into the cytosol binds and activates the enzyme cyclic-GMP-AMP synthase (cGAS), which produces 2'3'-cGAMP and triggers STING/TBK-1/IRF3 activation, resulting in type I IFN expression. Here, we reveal a cytosolic response to GC DNA that also contributes to type I IFN induction. We demonstrate that …

Beyond Bivariate Correlations: Three-Block Partial Least Squares Illustrated With Vegetation, Soil, And Topography, Daehyun Kim, Thomas J. Dewitt, César S. B. Costa, John A. Kupfer, Ryan W. Mcewan, J. Anthony Stallins

Ryan McEwan

Ecologists, particularly those engaged in biogeomorphic studies, often seek to connect data from three or more domains. Using three-block partial least squares regression, we present a procedure to quantify and define bi-variance and tri-variance of data blocks related to plant communities, their soil parameters, and topography. Bi-variance indicates the total amount of covariation between these three domains taken in pairs, whereas tri-variance refers to the common variance shared by all domains. We characterized relationships among three domains (plant communities, soil properties, topography) for a salt marsh, four coastal dunes, and two temperate forests spanning several regions in the world. We …

The Ifitms Inhibit Zika Virus Replication, George Savidis, Jill Perreira, Jocelyn M. Portmann, Paul Meraner, Zhiru Guo, Sharone Green, Abraham L. Brass

Sharone Green

Zika virus has emerged as a severe health threat with a rapidly expanding range. The IFITM family of restriction factors inhibits the replication of a broad range of viruses, including the closely related flaviruses West Nile virus and dengue virus. Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle. Moreover, IFITM3 can prevent Zika-virus-induced cell death. These results suggest that strategies to boost the actions and/or levels of the IFITMs might be useful for inhibiting a broad range of emerging viruses.

Identification Of Zika Virus And Dengue Virus Dependency Factors Using Functional Genomics, George Savidis, William M. Mcdougall, Paul Meraner, Jill Perreira, Jocelyn M. Portmann, Gaia Trincucci, Sinu P. John, Aaron M. Aker, Nicholas Renzette, Douglas R. Robbins, Zhiru Guo, Sharone Green, Timothy F. Kowalik, Abraham L. Brass

Sharone Green

The flaviviruses dengue virus (DENV) and Zika virus (ZIKV) are severe health threats with rapidly expanding ranges. To identify the host cell dependencies of DENV and ZIKV, we completed orthologous functional genomic screens using RNAi and CRISPR/Cas9 approaches. The screens recovered the ZIKV entry factor AXL as well as multiple host factors involved in endocytosis (RAB5C and RABGEF), heparin sulfation (NDST1 and EXT1), and transmembrane protein processing and maturation, including the endoplasmic reticulum membrane complex (EMC). We find that both flaviviruses require the EMC for their early stages of infection. Together, these studies generate a high-confidence, systems-wide view of human-flavivirus …

Patterning Defects In Silkworm Embryos Analysed Through Cuticle Preparations, Amit Singh, Madhuri Kango-Singh, K. P. Gopinathan

Madhuri Kango-Singh

The mulberry silkworm, Bombyx mori, a holometabolous lepidopteran insect, has a metameric body plan. Due to its functional adaptation, B. mori presents some unique deviations in its pal/ern from the evolutionarily advanced dipteran insect, Drosophila melanogaster. Previous studies on mutant phenotype analysis in B. mori have been carried out in late stages of larval development. Here we employ, the cuticle preparation approach during embryonic development to study morphological landmarks associated with B. mori, Eri, another race a/silkworm, and pattern defects associated with Ekp mutant of B.mori. The homeotic mutant Ekp, generates ectopic abdominallegs, a feature …

Eye Suppression, A Novel Function Of Teashirt, Requires Wingless Signaling, Amit Singh, Madhuri Kango-Singh, Y. Henry Sun

Madhuri Kango-Singh

Teashirt (tsh) encodes a Drosophila zinc-finger protein. Misexpression of tsh has been shown to induce ectopic eye formation in the antenna. We report that tsh can suppress eye development. This novel function of tsh is due to the induction of homothorax (hth), a known repressor of eye development, and requires Wingless (WG) signaling. Interestingly, tsh has different functions in the dorsal and ventral eye, suppressing eye development close to the ventral margin, while promoting eye development near the dorsal margin. It affects both growth of eye disc and retinal cell differentiation.

Lobe And Serrate Are Required For Cell Survival During Early Eye Development In Drosophila, Amit Singh, Xiao Shi, Kwang-Wook Choi

Amit Singh

Organogenesis involves an initial surge of cell proliferation, leading to differentiation. This is followed by cell death in order to remove extra cells. During early development, there is little or no cell death. However, there is a lack of information concerning the genes required for survival during the early cell-proliferation phase. Here, we show that Lobe (L) and the Notch (N) ligand Serrate (Ser), which are both involved in ventral eye growth, are required for cell survival in the early eye disc. We observed that the loss-of-ventral-eye phenotype in L or Ser mutants is due to …

The Hippo Pathway Effector Yki Downregulates Wg Signaling To Promote Retinal Differentiation In The Drosophila Eye, Erika Lynn Wittkorn, Ankita Sarkar, Kristine Garcia, Madhuri Kango-Singh, Amit Singh

Amit Singh

The evolutionarily conserved Hippo signaling pathway is known to regulate cell proliferation and maintain tissue homeostasis during development. We found that activation of Yorkie (Yki), the effector of the Hippo signaling pathway, causes separable effects on growth and differentiation of theDrosophila eye. We present evidence supporting a role for Yki in suppressing eye fate by downregulation of the core retinal determination genes. Other upstream regulators of the Hippo pathway mediate this effect of Yki on retinal differentiation. Here, we show that, in the developing eye, Yki can prevent retinal differentiation by blocking morphogenetic furrow (MF) progression and R8 specification. The …

Neurodegeneration - A Means To An End, Amit Singh

Amit Singh

Cell death, a global phenomenon found throughout the animal kingdom, is a mechanism to maintain tissue homeostasis and for adaptation to changes in the environment [1,2]. Millions of cells die in our body daily- they succumb to stress and commit suicide by a mechanism referred to as cell death or apoptosis [2-4]. Under normal conditions cells are continuously replaced by new cells from the stemor progenitor- cells. For example, an optimum balance in shedding of dead cells from the skin and their replenishment by new ones maintain our health and hygiene. In this context, apoptosis is a mechanism to eliminate …

Initial State Of The Drosophila Eye Before Dorsoventral Specification Is Equivalent To Ventral, Amit Singh, Kwang-Wook Choi

Amit Singh

Dorsoventral (DV) patterning is crucial for eye development in invertebrates and higher animals. DV lineage restriction is the primary event in undifferentiated early eye primordia of Drosophila. InDrosophila eye disc, a dorsal-specific GATA family transcription factor pannier (pnr) controls Iroquois-Complex (Iro-C) genes to establish the dorsal eye fate whereas Lobe (L), which is involved in controlling a Notch ligand Serrate (Ser), is specifically required for ventral growth. However, fate of eye disc cells before the onset of dorsal expression of pnr and Iro-C is not known. We show that L/Ser …

Cell Type-Specific Responses To Wingless, Hedgehog And Decapentaplegic Are Essential For Patterning Early Eye-Antenna Disc In Drosophila, Jong-Hoon Won, Orkhon Tsogtbartarr, Wonseok Son, Amit Singh, Kwang-Wook Choi, Kyung-Ok Cho

Amit Singh

The Drosophila eye-antenna imaginal disc (ead) is a flattened sac of two-layered epithelia, from which most head structures are derived. Secreted morphogens like Wingless (Wg), Hedgehog (Hh), and Decapentaplegic (Dpp) are important for early patterning of ead, but the underlying mechanisms are still largely unknown. To understand how these morphogens function in the ead of early larval stages, we used wg-LacZ and dpp-Gal4 markers for the examination of wild-type and mutant eads. We found that the ead immediately after hatching was crescent-shaped with the Bolwig’s nerve at the ventral edge, suggesting that it consists of dorsal domain. In a subsequent …