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Aug. 29, 2018

A Scientist Shows His Creative Flair for Turning Mentees Into Mentors

A Scientist Known for His Groundbreaking Research Turns Mentees Into Mentors

July 17, 2017

F1000 Article Recommendation (Very good)

Hydrogen sulphide (H2S) is a key signalling molecule in higher eukaryotes and is regarded as the third ‘gasotransmitter’ or small signalling molecule (after NO and CO). It regulates physiological processes in higher animals and is an antimicrobial agent. It is also generated endogenously in animals and microbes and in the latter has been shown to protect cells against antibiotics. Here Mironov and colleagues identify 3-mercaptopyruvate sulfurtransferase as the major source of H2S in E. coli; resistance to exogenous H2O2 is dependent on this enzyme. A model is proposed linking cysteine metabolism, H2S and oxidative stress.

Sept. 30, 2016

F1000 Prime

This study reports a novel role for bacterial small RNAs (sRNAs): preventing Rho-dependent transcription termination. Sedlyarova et al. demonstrate that many Escherichia coli genes contain long (>80nt) 5’UTRs that are sites of Rho termination.

Sept. 30, 2016

sRNA-Mediated Control of Transcription Termination in E. coli.

This study reports a novel role for bacterial small RNAs (sRNAs): preventing Rho-dependent transcription termination. Sedlyarova et al. demonstrate that many Escherichia coli genes contain long (>80nt) 5’UTRs that are sites of Rho termination.

Aug. 24, 2016

Fighting Antibiotic Resistance Through Deeper Sequencing

Researchers developed a new technique to uncover rare mutations in the bacterial genome and used it to determine how certain antibiotics mutate DNA. How will this approach help combat antibiotic resistance? Find out...

June 27, 2016

Exogenous Hsp70 delays senescence and improves cognitive function in aging mice.

The impressive takeaway messages of this publication are given in its title, that recombinant human Hsp70 (presumably the stress-induced form) can be administered intranasally as a therapeutic agent to maintain cognitive function and to extend lifespan in aging mice.

June 22, 2016

Sequencing method precise enough to reveal mechanisms by which bacteria resist antibiotics

A new technology can read the order (sequence) of the "letters" making up DNA code with enough accuracy to reveal how bacteria use high-speed evolution to defeat antibiotics. That is the finding of a study led by researchers at NYU Langone Medical Center and published June 22 in the journal Nature.

May 25, 2016

Factor Preserves DNA Integrity in Bacteria Despite Assault from Antibiotics

NEW YORK, May 19, 2016 /PRNewswire-USNewswire/ -- A key biochemical enables bacteria to repair otherwise fatal damage to their DNA, including that caused by antibiotics. That is the finding of a study led by researchers at NYU Langone Medical Center and published May 20 in the journal Science.

April 18, 2016

Chronic Exogenous Hsp70 Administration Has Cognitive, Behavioral, and Molecular Neuroprotective Effects on Aging Mice

Heat Shock Protein 70 (Hsp70) is a molecular chaperone that plays a protective role in various neurodegenerative disorders associated with aging, but its synthesis, induction, and activity in neuronal tissues decrease with age. As intranasally injected Hsp70 can enter murine neurons, Evgeny Nudler and his team explored the effect of exogenous Hsp70 on longevity

Sept. 15, 2014

Scientists Identify the Master Regulator of Cells’ Heat Shock Response, Pointing to New Potential Targets for Neurodegenerative Diseases and Cancer

Heat shock proteins protect the molecules in all human and animal cells with factors that regulate their production and work as thermostats. In new research published Sept. 16 in the journal eLife, scientists at NYU Langone Medical Center and elsewhere report for the first time that a protein called translation elongation factor eEF1A1 orchestrates the entire process of the heat shock response. By doing so, eEF1A1 supports overall protein homeostasis inside the cell, ensuring that it functions properly under various internal and external stress conditions. The researchers suggest that this finding could reveal a promising, new drug target for neurodegenerative diseases and cancer.

Feb. 11, 2014

DNA Damage Scout

Long known for its role in transcribing the genome’s code into messenger RNAs that can be translated into proteins, the enzyme RNA polymerase may also survey the genome for damage. That’s according to a study led by investigators at the New York University Langone Medical Center, which was published last month (January 8) in Nature. Biochemist Evgeny Nudler and his colleagues have described one way in which bacterial cells rely on RNA polymerase to start repairing DNA damage, which, the authors added, hint at pervasive transcription—the surprising revelation of noncoding RNA molecules and an axis of debate in molecular biology.

Jan. 21, 2014

UvrD facilitates DNA repair by pulling RNA polymerase backwards

Nucleotide excision repair is a DNA damage repair pathway that removes a variety of DNA lesions, including UV-induced thymine dimers. UvrD is a DNA-dependent DNA helicase required for nucleotide excision repair in E. coli. In this work, Epshtein et al. demonstrate that UvrD is an RNA polymerase-binding protein. The authors also show that UvrD promotes backwards sliding, or 'backtracking', of RNA polymerase at numerous positions along the DNA, an activity dependent on its ATP-binding motif.

Jan. 16, 2014

Molecular biology: The tug of DNA repair

The transcription enzyme RNA polymerase stalls at DNA lesions, hindering their repair. Accessory factors dislodge the enzyme by pushing it forwards, but a study finds that pulling it backwards may also be effective.

Jan. 9, 2014

Enzyme Reverses Stalled Transcription Machinery to Aid DNA Repair

Rather like a train halted by damaged rails is hauled away, the better to expose the rails to repair crews, RNA polymerase that is snagged by a faulty stretch of DNA can be pulled backwards by an enzyme, a transcription elongation factor with helicase/translocase activity. This enzyme appears to play an essential role in nucleotide excision repair, helping RNA polymerase backtrack when necessary, facilitating its transcriptional role, and even enabling it to serve a damage-scanning function.

Jan. 8, 2014

Molecular engines star in new model of DNA repair

Our health depends in large part upon the ability of specialized enzymes to find and repair the constant barrage of DNA damage brought on by ultraviolet light radiation and other sources. In a new study NYU School of Medicine researchers reveal how an enzyme called RNA polymerase patrols the genome for DNA damage and helps recruit partners to repair it. The result: fewer mutations and consequently less cancer and other kinds of disease.

March 15, 2013

F1000 evaluation

This article describes a very interesting example of interspecies signaling between commensal bacteria and their Caenorhabditis elegans worm host. This worm does not contain a gene encoding nitric oxide synthase (NOS) and, thus, does not produce NO via this enzyme. Bacteria that feed the worm provide the bacterial enzyme, resulting in the generation of NO. The worms show enhanced longevity and stress resistance as a result of NO-enhanced signaling via the HSF-1 and DAF-16 transcription factors.

Feb. 24, 2013

Study shows nitric oxide may increase life span Read more: http://www.digitaljournal.com/article/343375#ixzz2L4myjPHv

Research has shown that nitric oxide increases circulation and can be beneficial to those suffering from hypertension and congestive heart failure, but a new study suggests it may also increase our overall life span.

Feb. 14, 2013

Nitric Oxide: A Little Molecule's Remarkable Feat -- Prolonging Life, Worm Study Shows

Nitric oxide, the versatile gas that helps increase blood flow, transmit nerve signals, and regulate immune function, appears to perform one more biological feat -- prolonging the life of an organism and fortifying it against environmental stress, according to a new study.

April 11, 2012

Bacterial transcription: Rho gets to grips with the riboswitch

Riboswitches have emerged as an important class of regulatory elements that control the fate of bacterial mRNAs. These RNA structures are located upstream of the coding region of many mRNAs and, in response to the binding of specific metabolites or ions, the mRNA structure is altered, typically blocking expression of the encoded protein. Two general mechanisms of riboswitch action have previously been described; the first relies on the formation of an intrinsic transcription terminator, and the second on sequestration of the ribosome-binding site or start codon. Hollands et al. now show that a third general mechanism exists in both Salmonella enterica subsp. enterica serovar Typhimurium and Escherichia coli that uses the RNA helicase, Rho, to attenuate transcription.

Jan. 13, 2012

F1000 Evaluation

This thorough research surprisingly establishes a cytoprotectant role for hydrogen sulfide (H2S) production by non-sulfur bacteria growing aerobically. While this gas has been shown in mammals to have signaling properties that are similar to nitric oxide (NO), no apparent role for low levels of H2S had been demonstrated in bacteria. It had long been known that many bacteria produce low levels of H2S that were thought to be a byproduct of sulfur amino acid metabolism. Of special interest was the demonstration here that diverse species of pathogens were more resistant to antibiotics when producing H2S.

Jan. 13, 2012

F1000 Evaluation

This paper describes a structural model of the antibiotic tagetitoxin (Tgt) bound to the transcription elongation complex (TEC) of bacterial RNA polymerase, which was prepared by molecular dynamic simulation. This model proposed a new Tgt binding site, which is not the same one as found in the X-ray crystal structure of RNA polymerase {1}, and Tgt complex, and provides new insight into how Tgt inhibits RNA polymerase activity.

Jan. 2, 2012

Antimicrobials: Promoting tolerance

Tolerance to antibiotics in genetically susceptible bacteria poses major problems for the treatment of infectious diseases and provides a source of resistant strains. Two papers published in Science now provide insight into the diverse mechanisms underlying this process.

Nov. 18, 2011

New Clues for Improving Antibiotics for Tolerant Bacteria

Some of the ways bacteria protect themselves from antibiotics might be used against them to strengthen existing drugs

Nov. 18, 2011

Antioxidant Strategies to Tolerate Antibiotics

In living organisms, aerobic metabolism produces toxic reactive oxygen species (ROS) (1). Life can thus be seen as a balance between metabolic rate and a cell's ability to detoxify ROS. This understanding has led to intense public interest and increased consumption of dietary antioxidants. Although the effectiveness of antioxidant supplements is not yet established, there is no doubt that eukaryotic and prokaryotic cells have developed efficient endogenous antioxidant mechanisms (1, 2). On pages 982 and 986 of this issue, Nguyen et al. (3) and Shatalin et al. (4) describe two such mechanisms that confer antibiotic tolerance in bacteria.

Nov. 17, 2011

Targeting Bacterial Gas Defenses Allow for Increased Efficacy of Numerous Antibiotics

Although scientists have known for centuries that many bacteria produce hydrogen sulfide (H2S) it was thought to be simply a toxic by-product of cellular activity. Now, researchers at NYU School of Medicine have discovered H2S in fact plays a major role in protecting bacteria from the effects of numerous different antibiotics.

Oct. 14, 2011

Linking RNA polymerase backtracking to genome instability in E. coli.

In this report, Dutta and colleagues provide an explanation for how active translation maintains the integrity of the Escherichia coli genome. The authors find that clashes between the transcription and replication machinery cause double-strand breaks in E. coli due to RNA polymerase backtracking on the gene. These breaks are prevented by the Mfd helicase (a super family II helicase that removes stalled transcription elongation factors) during co-directional collisions but not during head-on collision between the transcription machinery and the replisome.

June 2, 2010

Cooperation between translating ribosomes and RNA polymerase in transcription elongation.

This elegant study demonstrates direct cooperation between ribosomes and RNA polymerase resulting in translation-transcription coupling in bacteria. The presented results suggest that translating ribosomes stimulate transcription by preventing backtracking of RNA polymerase.

April 23, 2010

Syntheses That Stay Together

An old principle of macromolecular biosynthesis in bacteria is that the speed of protein synthesis (translation) matches that of messenger RNA (mRNA) synthesis (transcription), but how this integration occurs has not been clearly defined. An obvious conjecture is that ribosomes move along the emerging mRNA at whatever speed RNA polymerase goes so that translation and transcription remain coordinated, as it is known to do when conditions change (1). However, on page 504 (2) and 501 (3) of this issue, Proshkin et al. and Burmann et al., respectively, suggest the opposite: Efficient binding and progression of ribosomes along mRNA increase the speed of RNA polymerase, whereas the absence of ribosomes allows the polymerase to slow and wait for ribosomes to catch up.

Feb. 5, 2010

Rho and RNAP Finally Tie the Knot

Could allostery also be critical for Rho-dependent transcription termination in bacteria? The RNA helicase Rho uses the energy of ATP hydrolysis to move along an emerging nascent strand of RNA. When Rho reaches an actively transcribing RNA polymerase (RNAP), it disrupts elongation, and the RNAP molecule falls off the template DNA. Recent X-ray structures of Rho in a complex with RNA provide stunning details of Rho's translocation mechanism, but how Rho forces RNAP to dissociate from DNA and RNA is still unknown. Now, Epshtein et al. (2010) present compelling evidence that RNAP plays an active role in Rho-dependent termination.

Jan. 13, 2010

Paradigm Changing Mechanism Is Revealed for the Control of Gene Expression in Bacteria

A new study led by researchers at NYU Langone Medical Center is shedding new light on the action of Rho, a key regulatory protein in E. coli and many other bacteria. The study published in the January 14, 2010 issue of Nature reveals a new paradigm to understand the molecular principles of gene transcription. This work could potentially lead to the development of new types of antibiotics that could target Rho and its crucial functions.

Jan. 10, 2010

When It Comes to Antibiotics, Bacteria Show Some NO-how

Homologs to mammalian nitric oxide synthases are found in many mostly Gram-positive bacteria. In some genera such as bacilli, and staphylococci, the NO these enzymes produce protects against oxidative damage, this effect has now been shown to provide an advantage against antibiotics that kill by increasing cellular levels of reactive oxygen species.

Oct. 1, 2009

F1000 Evaluation

In this landmark study Gusarov et al. demonstrate that loss of the nitric oxide synthase (NOS) gene in Bacillus subtilis renders the bacteria hypersusceptible to a diverse panel of antimicrobials, including classical antibiotics. Bacterial NOS, therefore, represents a novel target for antibiotic development, which is an important issue in this age of multidrug resistant bacteria.

Sept. 14, 2009

Bacteria Say NO To Drugs

Many species of bacteria express enzymes that synthesize nitric oxide (NO) from arginine, but so far the physiological role of such bacterial NO synthases has been a mystery. Now, Evgeny Nudler and colleagues at New York University School of Medicine have shown that endogenously produced NO protects bacteria from a broad spectrum of natural and synthetic antibiotics (Science 2009, 325, 1380). Their results suggest that inhibiting NO synthase in disease-causing bacteria could enhance the efficacy of antimicrobial therapy.

Sept. 11, 2009

Scientists Find Way To Make Bacteria More Vulnerable To Existing Antibiotics

A team of scientists in the US reports they may have a found a new way to make bacteria like MRSA and anthrax more vulnerable to existing antibiotics by interfering with a defence mechanism that the microbes use to resist the oxidative stress imposed on them by antibiotics.

Sept. 11, 2009

NO Good: Nitric Oxide May Be Key to Overcoming Antibiotic Resistance

Researchers may be a touch closer to eliminating antibiotic-resistant bacteria, such as MRSA (methicillin-resistant Staphylococcus aureus) and anthrax, thanks to a troublesome air pollutant—nitric oxide (NO).

Sept. 10, 2009

Study exposes how bacteria resist antibiotics

Scientists have discovered how bacteria fend off a wide range of antibiotics, and blocking that defense mechanism could give existing antibiotics more power to fight dangerous infections.

June 27, 2008

Microbiology Select

Bacteria are one of the most diverse groups of organisms on our planet and are exquisitely adapted for survival in diverse environments ranging from the human digestive tract to deep-sea hydrothermal vents. As bacteria have evolved to optimally inhabit and exploit their host environments, so too have their hosts changed in response to the presence of these prokaryote interlopers. This issue's Microbiology Select highlights recent findings that shed light on the interactions of bacteria with their environments as well as the beneficial contributions that some bacteria make to their hosts.

May 15, 2008

An Ancient Protein Balances Gene Activity And Silences Foreign DNA In Bacteria

Compared to humans, bacteria have a much tidier genome. The tiny microorganisms pack their genes closely together, and don't carry around a lot of extraneous DNA, so-called junk DNA that fills in the gaps between genes. Some 90 percent of the complete genome sequence of the bacteria E. coli contains sequences of DNA that code for protein, while 90 percent of the human genome is non--coding junk DNA.

Jan. 24, 2008

Weakness Identified In Anthrax Bacteria

MIT and New York University researchers have identified a weakness in the defenses of the anthrax bacterium that could be exploited to produce new antibiotics.

Jan. 20, 2008

No way out for anthrax?

Nitric oxide (NO), a chemical “weapon” produced by phagocytic cells of the immune system (macrophages), is part of the first wave of defense against invading pathogens such as Bacillus anthracis, the anthrax bacterium. With the aid of an intracellular fluorescent sensor for the chemical, however, Konstantin Shatalin et al. have found that NO may actually help the bacterium evade the immune system and protect it from attack.

Oct. 10, 2006

The logic of sharing

By implementing a systematic chromatin immunoprecipitation-microarray (ChIP-chip) analysis of the heat-shock σ-factor regulon (σ32) of Escherchia coli, Wade et al. reveal the surprising finding that there is functional overlap between σ factors.Sigma factors confer specificity on the bacterial RNA polymerase (RNAP), directing this enzyme to promoter sequences, positioning the RNAP at the promoter and effecting local unwinding of the DNA duplex near to the transcription start site.

May 19, 2006

Biochemistry

5th edition

Feb. 18, 2005

A ratchet mechanism of transcription elongation and its control.

This article revolutionizes our understanding of the catalytic mechanism of multisubunit RNA polymerases by showing, using elegant biochemical experiments, that transcript elongation operates through a complex ratchet mechanism.

Jan. 28, 2005

Machinations of a Maxwellian Demon

The mechanisms by which RNA polymerase moves along DNA during elongation have been difficult to determine experimentally. In this issue of Cell, Bar-Nahum et al. (2005) show that back and forth sliding of RNA polymerase on DNA may be coupled to bending of an α helix, which can alternately occlude and expose the NTP binding site. Transcription factors can regulate elongation by modulating this bending motion.

Nov. 22, 2004

Issue highlight

The development of blood substitutes originally focused on heme-based compounds; however, this class of agents was problematic, in part because of their tendency to degrade nitric oxide (NO), an important endothelial product that prevents vasospasm and thrombosis. In the search for blood substitutes, perfluorocarbons recently have emerged as a promising class of compounds, largely as a result of their transport capacity for both oxygen and carbon dioxide. Rafikova and colleagues report in this issue of Circulation that perfluorocarbons offer the additional advantage of transporting NO and preserving its actions in the bloodstream

March 19, 2004

Molecular Biology (2004 3rd edition)

Third edition

Dec. 17, 2003

Transcription through the roadblocks: the role of RNA polymerase cooperation.

This paper provides evidence that tandemly transcribing RNA polymerases cooperate to increase the overall efficiency of elongation.

Dec. 15, 2003

Genes VIII

For courses in Molecular Biology, Molecular Genetics, and Gene Regulation. Two decades ago Benjamin Lewin's Genes revolutionized the teaching of molecular biology and molecular genetics by introducing a unified approach to bacteria and higher organisms. Genes has remained at the cutting edge of molecular biology, covering gene structure, organization, and expression. Originally the text opened with the genetic code and worked toward genome structure. Genes VIII changed the approach to begin with the sequence of the human and other genomes and starts with complete coverage of recent advances in genomics. The coverage of genomics is then integrated throughout the text. In striving to maintain currency, the new edition has updated coverage on genome organization, DNA replication, gene regulation and many other new topics.

Oct. 11, 2003

ASM News

ASM News 70 (3) 113-114

April 25, 2003

Genes VIII

For courses in Molecular Biology, Molecular Genetics, and Gene Regulation. Two decades ago Benjamin Lewin's Genes revolutionized the teaching of molecular biology and molecular genetics by introducing a unified approach to bacteria and higher organisms. Genes has remained at the cutting edge of molecular biology, covering gene structure, organization, and expression. Originally the text opened with the genetic code and worked toward genome structure. Genes VIII changed the approach to begin with the sequence of the human and other genomes and starts with complete coverage of recent advances in genomics. The coverage of genomics is then integrated throughout the text. In striving to maintain currency, the new edition has updated coverage on genome organization, DNA replication, gene regulation and many other new topics.

April 25, 2003

The riboswitch-mediated control of sulfur metabolism in bacteria.

A direct experiment demonstrating, in an in vitro reaction with purified components, the action of a "riboswitch", i.e., the element on the nascent RNA transcript that controls a biological process by directly sensing the effector compound in the environment.

Jan. 22, 2003

Sensing small molecules by nascent RNA: a mechanism to control transcription in bacteria.

Reports that formation of a specific complex between thiamin and riboflavin, and a conserved leader region of mRNA coding for thiamin and riboflavin biosynthetic factors, leads to a novel transcriptional regulatory mechanism.

Jan. 1, 2003

Gene regulation: Small but perfectly ... regulating

One way for bacteria to modulate their gene expression is by attenuation — by which structural changes in the 5' leader of a transcript bring about transcription termination of downstream genes in the same operon. In most cases, a ribosome, an RNA binding protein or an uncharged tRNA can alter RNA structure so that the so-called terminator loop doesn't form; instead, the alternative structure (referred to as the antiterminator) allows transcription to proceed. Now, Mironov et al. uncover a new mechanism of attenuation. They show that, in Bacillus, some small molecules can regulate their own transcription by interacting directly with specific sequences on RNAs that are transcribed from the operon to which they belong.

Dec. 1, 2002

Take Your Vitamins with a Pinch of RNA

RNA “aptamers” capable of binding and discriminating among structurally related small molecules can be concocted in the laboratory. Two groups have now discovered that conserved domains in the 5′ ends of some mRNAs bind specific metabolites and respond by changing their shape in biologically useful ways, demonstrating that aptamers also are present in the natural world.

Jan. 24, 2002

Isolation and characterization of sigma(70)-retaining transcription elongation complexes from Escherichia coli.

Contrary to the 'sigma cycle' model of transcription initiation, this paper demonstrates that a significant fraction of the RNA polymerase in Escherichia coli retain sigma-70 during the elongation cycle and that this fraction reaches its maximum upon entry of cells into stationary phase.

Sept. 14, 2001

Sigma Holds On

Many decades of work have provided details of the molecular mechanism and machinery needed for prokaryotic gene expression. Bacterial genes are transcribed by the RNA polymerase enzyme, which associates with a sigma subunit during transcription initiation. Afterwards, the sigma subunit is released from the polymerase and an elongation factor, NusA, binds. NusA remains bound to the polymerase throughout transcription elongation and termination and is then removed to allow sigma to bind once again for transcription re-initiation. This is termed the “sigma cycle.”

Jan. 1, 1999

Molecular Biology (1999 First Edition)

First edition