TAMM HORSFALL PROTEIN: THE MEN BEHIND THE EPONYM

Tamm–Horsfall Protein (uromodulin) is named after Igor Tamm and Franc Horsfall Jr who described it for the first time in 1952. It is a glycoprotein, secreted by the cells in the thick ascending limb of the loop of Henle. This protein will perform a number of important pathophysiological functions, including protection against uroinfections, especially caused by E. Сoli, and protection against formation of calcium concernments in the kidney. Igor Tamm (1922-1995) is an outstanding cytologist, virologist and biochemist. He is one of the pioneers in the study of viral replication. He was born in Estonia and died in the USA. In 1964 he was elected for a professorship in Rockefeller Institute for Medical Research, where has been working continuously. Since 1959, he became a head of the virology lab established by his mentor and co-author Franc Horsfall. In the course of studies on the natural inhibitor of viral replication, Tamm and Horsfall isolated and characterized biochemically a new protein named after their names. Franc Lappin Horsfall Jr (1906-1971) was a well-known clinician and virologist with remarkable achievements in internal medicine. He was born and died in the USA. He worked in the Rockefeller Hospital from 1934 to 1960, then in the Center for Cancer Research at the Sloan-Kettering Institute. Here he was a leader of a research team studying the molecular mechanisms of immunity, the effects of chemotherapy with benzimidazole compounds (together with I. Tamm), coxsackie viruses, herpes simplex virus, etc.

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Nucleolin Is Required for an Efficient Herpes Simplex Virus Type 1 Infection

Journal of Virology ◽

10.1128/jvi.00077-08 ◽

2008 ◽

Vol 82 (10) ◽

pp. 4762-4773 ◽

Cited By ~ 57

Author(s):

Aleth Callé ◽

Iva Ugrinova ◽

Alberto L. Epstein ◽

Philippe Bouvet ◽

Jean-Jacques Diaz ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Viral Replication ◽

Virus Type ◽

Herpes Simplex Virus Type ◽

Nucleolar Protein ◽

Simplex Virus ◽

First Time ◽

Hsv 1

ABSTRACT Productive infection by herpes simplex virus type 1 (HSV-1), which occurs in the host cell nucleus, is accompanied by dramatic modifications of the nuclear architecture, including profound alterations of nucleolar morphology. Here, we show that the three most abundant nucleolar proteins—nucleolin, B23, and fibrillarin—are redistributed out of the nucleoli as a consequence of HSV-1 infection. We show that the amount of nucleolin increases progressively during the course of infection. We demonstrate for the first time that a nucleolar protein, i.e., nucleolin, colocalizes with ICP8 in the viral replication compartments, at the time when viral replication is effective, suggesting an involvement of nucleolin in the HSV-1 DNA replication process. At later times of infection, a granular form of nucleolin localizes to the cytoplasm, in structures that display the characteristic features of aggresomes, indicating that this form of nucleolin is very probably destined for degradation. The delocalization of nucleolin from the nucleoli requires the viral ICP4 protein or a factor(s) whose expression involves ICP4. Using small interfering RNA technology, we show that viral replication requires a high level of nucleolin expression, demonstrating for the first time a direct role for a nucleolar protein in herpes simplex virus biology.

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Antiviral Action of Hydromethanolic Extract of Geopropolis fromScaptotrigona posticaagainst Antiherpes Simplex Virus (HSV-1)

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/296086 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 13

Author(s):

Guilherme Rabelo Coelho ◽

Ronaldo Zucatelli Mendonça ◽

Karina de Senna Vilar ◽

Cristina Adelaide Figueiredo ◽

Juliana Cuoco Badari ◽

...

Keyword(s):

Electron Microscopy ◽

Antiviral Activity ◽

Viral Replication ◽

Viral Dna ◽

Replication Complex ◽

Transmission Electron ◽

Scaptotrigona Postica ◽

Simplex Virus ◽

First Time

The studies on chemical composition and biological activity of propolis had focused mainly on speciesApis melliferaL. (Hymenoptera: Apidae). There are few studies about the uncommon propolis collected by stingless bees of the Meliponini tribe known as geopropolis. The geopropolis fromScaptotrigona posticawas collected in the region of Barra do Corda, Maranhão state, Brazil. The chemical analysis of hydromethanolic extract of this geopropolis (HMG) was carried out through HPLC-DAD-ESI-MS/MS and the main constituents found were pyrrolizidine alkaloids and C-glycosyl flavones. The presence of alkaloids in extracts of propolis is detected for the first time in this sample. The antiviral activity of HMG was evaluated through viral DNA quantification experiments and electron microscopy experiments. Quantification of viral DNA from herpes virus showed reduction of about 98% in all conditions and concentration tested of the HMG extract. The results obtained were corroborated by transmission electron microscopy, in which the images did not show particle or viral replication complex. The antiviral activity of C-glycosyl flavones was reported for a variety of viruses, being observed at different points in the viral replication. This work is the first report about the antiviral activity of geopropolis fromScaptotrigona postica, in vitro, against antiherpes simplex virus (HSV).

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Combining QTL Mapping and Gene Expression Analysis to Elucidate the Genetic Control of ‘Crumbly’ Fruit in Red Raspberry (Rubus idaeus L.)

Agronomy ◽

10.3390/agronomy11040794 ◽

2021 ◽

Vol 11 (4) ◽

pp. 794

Author(s):

Luca M. Scolari ◽

Robert D. Hancock ◽

Pete E. Hedley ◽

Jenny Morris ◽

Kay Smith ◽

...

Keyword(s):

Genetic Control ◽

Developmental Disorder ◽

Molecular Mechanisms ◽

Developmental Stages ◽

Microarray Experiment ◽

Rubus Idaeus ◽

Red Raspberry ◽

Genotype By Sequencing ◽

First Time ◽

Selection Of

‘Crumbly’ fruit is a developmental disorder in raspberry that results in malformed and unsaleable fruits. For the first time, we define two distinct crumbly phenotypes as part of this work. A consistent crumbly fruit phenotype affecting the majority of fruits every season, which we refer to as crumbly fruit disorder (CFD) and a second phenotype where symptoms vary across seasons as malformed fruit disorder (MFD). Here, segregation of crumbly fruit of the MFD phenotype was examined in a full-sib family and three QTL (Quantitative Trait Loci) were identified on a high density GbS (Genotype by Sequencing) linkage map. This included a new QTL and more accurate location of two previously identified QTLs. A microarray experiment using normal and crumbly fruit at three different developmental stages identified several genes that were differentially expressed between the crumbly and non-crumbly phenotypes within the three QTL. Analysis of gene function highlighted the importance of processes that compromise ovule fertilization as triggers of crumbly fruit. These candidate genes provided insights regarding the molecular mechanisms involved in the genetic control of crumbly fruit in red raspberry. This study will contribute to new breeding strategies and diagnostics through the selection of molecular markers associated with the crumbly trait.

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Analysis of a Preliminary microRNA Expression Signature in a Human Telangiectatic Osteogenic Sarcoma Cancer Cell Line

International Journal of Molecular Sciences ◽

10.3390/ijms22031163 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1163

Author(s):

Gaia Palmini ◽

Cecilia Romagnoli ◽

Simone Donati ◽

Roberto Zonefrati ◽

Gianna Galli ◽

...

Keyword(s):

Cell Line ◽

Molecular Mechanisms ◽

Osteogenic Sarcoma ◽

Cancer Cell Line ◽

Microscopic Features ◽

In Vitro Establishment ◽

Profile Characteristic ◽

First Time

Telangiectatic osteosarcoma (TOS) is an aggressive variant of osteosarcoma (OS) with distinctive radiographic, gross, microscopic features, and prognostic implications. Despite several studies on OS, we are still far from understanding the molecular mechanisms of TOS. In recent years, many studies have demonstrated not only that microRNAs (miRNAs) are involved in OS tumorigenesis, development, and metastasis, but also that the presence in high-grade types of OS of cancer stem cells (CSCs) plays an important role in tumor progression. Despite these findings, nothing has been described previously about the expression of miRNAs and the presence of CSCs in human TOS. Therefore, we have isolated/characterized a putative CSC cell line from human TOS (TOS-CSCs) and evaluated the expression levels of several miRNAs in TOS-CSCs using real-time quantitative assays. We show, for the first time, the existence of CSCs in human TOS, highlighting the in vitro establishment of this unique stabilized cell line and an identification of a preliminary expression of the miRNA profile, characteristic of TOS-CSCs. These findings represent an important step in the study of the biology of one of the most aggressive variants of OS and the role of miRNAs in TOS-CSC behavior.

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Student loan debt and first-time home buying in USA

International Journal of Housing Markets and Analysis ◽

10.1108/ijhma-09-2020-0118 ◽

2021 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Robert H. Scott III ◽

Steven Bloom

Keyword(s):

College Graduates ◽

Student Loans ◽

Student Loan ◽

Home Equity ◽

Student Loan Debt ◽

Content Type ◽

Loan Debt ◽

The Usa ◽

First Time ◽

Home Buying

Purpose This paper aims to examine the relationship between student loan debt and first-time home buying among college graduates aged 23 to 40 years old in the USA. Design/methodology/approach The authors use the Federal Reserve’s 2019 Survey of Consumer Finances data on American households to present descriptive statistics and run logistic regressions that measure the effects of student loan debt on first-time home buying. The authors also present original survey data of mortgage lenders that provides an industry-level perspective. Findings The authors find that having student loan debt does not by itself prohibit first-time home buyers. On the contrary, having student loan debt increases the likelihood of homeownership by 15.1%. People with student loan debt, however, buy homes that are 39.2% less expensive and have 58% less home equity compared to first-time home buyers without student loans. In addition, it is found that the amount of student loan debt is important. People with student loan debt above the median amount among people with student loan debt ($35,000) are 27% less likely to be first-time home buyers. Practical implications This paper provides public policy analysts and other researchers a different perspective on the correlation between student loan debt and home buying. This study focuses narrowly on first-time home buyers who are college graduates between 23 and 40 years. Thus, capturing the youngest cohort of first-time home buyers and examine the primary factors that influence their home buying decisions. Originality/value First-time homebuyers are historically the largest segment of home buyers making them an important subcategory to study. The rise in student loan debt is posited to explain declining homeownership among younger people. The current literature on student loan debt and home buying often studies samples that are too heterogeneous resulting in mixed findings. This paper adds to the existing literature by filtering the sample to study the effects of student loan debt and first-time home buying among people with at least a college degree who are between 23 and 40 years.

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Herpesvirus-mediated stabilization of ICP0 expression neutralizes restriction by TRIM23

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2113060118 ◽

2021 ◽

Vol 118 (51) ◽

pp. e2113060118

Author(s):

Xing Liu ◽

Dhiraj Acharya ◽

Eric Krawczyk ◽

Chase Kangas ◽

Michaela U. Gack ◽

...

Keyword(s):

Viral Replication ◽

Viral Gene Expression ◽

Proteasomal Degradation ◽

Viral Gene ◽

Posttranslational Regulation ◽

Early Proteins ◽

Immediate Early Proteins ◽

Simplex Virus ◽

Functional Analyses ◽

Hsv 1

Herpes simplex virus (HSV) infection relies on immediate early proteins that initiate viral replication. Among them, ICP0 is known, for many years, to facilitate the onset of viral gene expression and reactivation from latency. However, how ICP0 itself is regulated remains elusive. Through genetic analyses, we identify that the viral γ134.5 protein, an HSV virulence factor, interacts with and prevents ICP0 from proteasomal degradation. Furthermore, we show that the host E3 ligase TRIM23, recently shown to restrict the replication of HSV-1 (and certain other viruses) by inducing autophagy, triggers the proteasomal degradation of ICP0 via K11- and K48-linked ubiquitination. Functional analyses reveal that the γ134.5 protein binds to and inactivates TRIM23 through blockade of K27-linked TRIM23 autoubiquitination. Deletion of γ134.5 or ICP0 in a recombinant HSV-1 impairs viral replication, whereas ablation of TRIM23 markedly rescues viral growth. Herein, we show that TRIM23, apart from its role in autophagy-mediated HSV-1 restriction, down-regulates ICP0, whereas viral γ134.5 functions to disable TRIM23. Together, these results demonstrate that posttranslational regulation of ICP0 by virus and host factors determines the outcome of HSV-1 infection.

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Taxonomic changes in Ichneumonoidea (Hymenoptera), and notes on certain type specimens

Zootaxa ◽

10.11646/zootaxa.4941.4.3 ◽

2021 ◽

Vol 4941 (4) ◽

pp. 511-541

Author(s):

GAVIN R. BROAD

Keyword(s):

New Combinations ◽

Type Specimens ◽

The Usa ◽

Taxonomic Changes ◽

First Time

The following new synonymies are established: Acrodactyla iliensis Sheng & Bian 1996 = Acrodactyla lachryma Pham, Broad, Matsumoto & Böhme 2012, syn. nov.; Euceros Gravenhorst 1829 = Lentocerus Dong & Naito 1999, syn. nov.; Euceros pruinosus (Gravenhorst 1829) = Lentocerus dentatus Dong & Naito 1999, syn. nov.; Euceros sensibus Uchida 1930 = Lentocerus lijiangensis Dong & Naito 1999, syn. nov.; Gyroneuron Kokujev 1901 = Cyclophatnus Cameron 1910, syn. nov.; Gyroneuron flavum (Cameron 1910) = Gyroneuron testaceator Watanabe 1934, syn. nov.; Liotryphon strobilellae (Linnaeus 1758) = Townesia qinghaiensis He 1996, syn. nov. The following are new combinations: Aleiodes insignis (Brues 1926), Aleiodes lateralis (Cameron 1905), Aleiodes maculicornis (Brues 1926), Aleiodes siccitesta (Morley 1937), Cyclophatnus flavum (Cameron 1910), Rhaconotus striatulus (Cameron 1909), Tolonus cingulatorius (Morley 1912), Zatypota tropica (Morley 1912). Netelia morleyi Townes, Townes & Gupta 1961 is transferred from the subgenus Netelia Gray 1860 to the subgenus Paropheltes Cameron 1907. One new replacement name is proposed: Aleiodes philippinensis nom. nov. for Rhogas lateralis Baker 1917, nec Troporhogas lateralis Cameron 1905. Lectotypes are designated for Antrusa persimilis Nixon 1954, Rhyssalus striatulus Cameron 1909, Troporhogas trimaculata Cameron 1905, Hemiteles cingulatorius Morley 1912, Paniscus ferrugineus Cameron 1889 and for Xanthojoppa inermis Morley 1917. Some previously overlooked type specimens are interpreted and illustrated and some errors in the literature corrected. Hosts are recorded for two genera of Ichneumoninae for the first time: Catadelphops nasutus (Heinrich 1962) was reared from Proserpinus terlooii (Edwards 1875) (Lepidoptera: Sphingidae) in the USA, and Aethianoplis excavata (Roman 1910) was reared from Precis octavia (Cramer 1777) (Lepidoptera: Nymphalidae) in Uganda.

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A Domain of Herpes Simplex Virus pUL33 Required To Release Monomeric Viral Genomes from Cleaved Concatemeric DNA

Journal of Virology ◽

10.1128/jvi.00854-17 ◽

2017 ◽

Vol 91 (20) ◽

Cited By ~ 4

Author(s):

Kui Yang ◽

Xiaoqun Dang ◽

Joel D. Baines

Keyword(s):

Amino Acids ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Viral Replication ◽

Dna Cleavage ◽

Artificial Chromosome ◽

Viral Dna ◽

Viral Genomes ◽

C Terminus ◽

Simplex Virus

ABSTRACT Monomeric herpesvirus DNA is cleaved from concatemers and inserted into preformed capsids through the actions of the viral terminase. The terminase of herpes simplex virus (HSV) is composed of three subunits encoded by UL15, UL28, and UL33. The UL33-encoded protein (pUL33) interacts with pUL28, but its precise role in the DNA cleavage and packaging reaction is unclear. To investigate the function of pUL33, we generated a panel of recombinant viruses with either deletions or substitutions in the most conserved regions of UL33 using a bacterial artificial chromosome system. Deletion of 11 amino acids (residues 50 to 60 or residues 110 to 120) precluded viral replication, whereas the truncation of the last 10 amino acids from the pUL33 C terminus did not affect viral replication or the interaction of pUL33 with pUL28. Mutations that replaced the lysine at codon 110 and the arginine at codon 111 with alanine codons failed to replicate, and the pUL33 mutant interacted with pUL28 less efficiently. Interestingly, genomic termini of the large (L) and small (S) components were detected readily in cells infected with these mutants, indicating that concatemeric DNA was cleaved efficiently. However, the release of monomeric genomes as assessed by pulsed-field gel electrophoresis was greatly diminished, and DNA-containing capsids were not observed. These results suggest that pUL33 is necessary for one of the two viral DNA cleavage events required to release individual genomes from concatemeric viral DNA. IMPORTANCE This paper shows a role for pUL33 in one of the two DNA cleavage events required to release monomeric genomes from concatemeric viral DNA. This is the first time that such a phenotype has been observed and is the first identification of a function of this protein relevant to DNA packaging other than its interaction with other terminase components.

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100 years of Rous sarcoma virus

Journal of Experimental Medicine ◽

10.1084/jem.20112160 ◽

2011 ◽

Vol 208 (12) ◽

pp. 2351-2355 ◽

Cited By ~ 60

Author(s):

Robin A. Weiss ◽

Peter K. Vogt

Keyword(s):

Rous Sarcoma Virus ◽

Molecular Mechanisms ◽

Experimental Medicine ◽

Research Career ◽

Rockefeller Institute ◽

Rous Sarcoma ◽

Sarcoma Virus ◽

Mechanisms Of Carcinogenesis ◽

Infectious Etiology

The discovery of Rous sarcoma virus, which was reported by Peyton Rous in the Journal of Experimental Medicine 100 years ago, opened the field of tumor virology. It showed that some cancers have infectious etiology, led to the discovery of oncogenes, and laid the foundation for the molecular mechanisms of carcinogenesis. Rous spent his entire research career at The Rockefeller Institute, and he was the JEM’s longest serving editor. Here, we comment briefly on the life of this remarkable scientist and on the importance of his discoveries.

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Identification of a PGXPP degron motif in dishevelled and structural basis for its binding to the E3 ligase KLHL12

Open Biology ◽

10.1098/rsob.200041 ◽

2020 ◽

Vol 10 (6) ◽

pp. 200041 ◽

Cited By ~ 1

Author(s):

Zhuoyao Chen ◽

Gregory A. Wasney ◽

Sarah Picaud ◽

Panagis Filippakopoulos ◽

Masoud Vedadi ◽

...

Keyword(s):

Ubiquitin Ligase ◽

Molecular Mechanisms ◽

Hydrophobic Interactions ◽

E3 Ubiquitin Ligase ◽

Structural Basis ◽

E3 Ligases ◽

Kelch Domain ◽

Ring E3 Ligases ◽

Ring E3 ◽

New Protein

Wnt signalling is dependent on dishevelled proteins (DVL1-3), which assemble an intracellular Wnt signalosome at the plasma membrane. The levels of DVL1-3 are regulated by multiple Cullin-RING E3 ligases that mediate their ubiquitination and degradation. The BTB-Kelch protein KLHL12 was the first E3 ubiquitin ligase to be identified for DVL1-3, but the molecular mechanisms determining its substrate interactions have remained unknown. Here, we mapped the interaction of DVL1-3 to a ‘PGXPP' motif that is conserved in other known partners and substrates of KLHL12, including PLEKHA4, PEF1, SEC31 and DRD4. To determine the binding mechanism, we solved a 2.4 Å crystal structure of the Kelch domain of KLHL12 in complex with a DVL1 peptide that bound with low micromolar affinity. The DVL1 substrate adopted a U-shaped turn conformation that enabled hydrophobic interactions with all six blades of the Kelch domain β-propeller. In cells, the mutation or deletion of this motif reduced the binding and ubiquitination of DVL1 and increased its stability confirming this sequence as a degron motif for KLHL12 recruitment. These results define the molecular mechanisms determining DVL regulation by KLHL12 and establish the KLHL12 Kelch domain as a new protein interaction module for a novel proline-rich motif.

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