208 research outputs found
Class I DISARM provides anti-phage and anti-conjugation activity by unmethylated DNA recognition
No full textBacteriophages impose a strong evolutionary pressure on microbes for the development of mechanisms of survival. Multiple new mechanisms of innate defense have been described recently, with the molecular mechanism of most of them remaining uncharacterized. Here, we show that a Class 1 DISARM (defense island system associated with restriction-modification) system from Serratia sp. provides broad protection from double-stranded DNA phages, and drives a population of single-stranded phages to extinction. We identify that protection is not abolished by deletion of individual DISARM genes and that the absence of methylase genes drmMI and drmMII does not result in autoimmunity. In addition to antiphage activity we also observe that DISARM limits conjugation, and this activity is linked to the number of methylase cognate sites in the plasmid. Overall, we show that Class 1 DISARM provides robust anti-phage and anti-plasmid protection mediated primarily by drmA and drmB, which provide resistance to invading nucleic acids using a mechanism enhanced by the recognition of unmethylated cognate sites of the two methylases drmMI and drmMII
Assessment of hemostatic profile in neonates with necrotizing enterocolitis using Rotational Thromboelastometry (ROTEM)
No full textBackground: This study aimed to explore the hemostatic profile of neonates with necrotizing enterocolitis (NEC) using Rotational Thromboelastometry (ROTEM) and to investigate if ROTEM parameters have the capacity to play a role in the differentiation of NEC from sepsis at the disease onset. Methods: This observational study included 62 neonates (mean gestational age 31.6 weeks and mean birth weight 1620g) hospitalized in a neonatal intensive care unit. The neonates were categorized in three groups: neonates with NEC (Bell stage II and above), neonates with sepsis and healthy neonates and they were matched 1:1:1 with regards to gestational age, delivery mode, and sex. Clinical, laboratory data as well as measurements of ROTEM parameters at disease onset were recorded. Results: ROTEM parameters differed between neonates with NEC and neonates with sepsis, indicating that NEC results in accelerated clot formation and higher clot strength compared to sepsis. The EXTEM CFT and A10 parameters demonstrated the highest diagnostic performance for NEC in terms of discrimination between NEC and sepsis (AUC, 0.997; 95% CI: 0.991–1.000 and 0.973; 95% CI: 0.932–1.000, respectively). Conclusions: Neonates with NEC manifested accelerated clot formation and higher clot strength compared to septic and healthy neonates, as these were expressed by ROTEM parameters. Impact: This work reports data on the hemostatic profile of neonates with necrotizing enterocolitis (NEC) using Rotational Thromboelastometry (ROTEM) and the capacity of ROTEM parameters in differentiating of NEC from sepsis at the disease onset. Neonates with NEC present acceleration of coagulation and exhibit a hypercoagulable profile, as this is expressed by ROTEM parameters, in comparison to septic and healthy neonates. ROTEM parameters demonstrated a good diagnostic capacity in differentiating NEC from sepsis at the disease onset. © The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc 2023
How Prevalent is Functional Alternative Splicing in the
No full textthis article can be found at doi: 10.1016/j.tig.2003.12.004 Corresponding author: Gil Ast ([email protected]
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Genome-wide experimental determination of barriers to horizontal gene transfer
No full textHorizontal gene transfer, in which genetic material is transferred from the genome of one organism to another, has been investigated in microbial species mainly through computational sequence analyses. To address the lack of experimental data, we studied the attempted movement of 246,045 genes from 79 prokaryotic genomes into E. coli and identified genes that consistently fail to transfer. We studied the mechanisms underlying transfer inhibition by placing coding regions from different species under the control of inducible promoters. Their toxicity to the host inhibited transfer regardless of the species of origin and our data suggest that increased gene dosage and associated increased expression is a predominant cause for transfer failure. While these experimental studies examined transfer solely into E. coli, a computational analysis of gene transfer rates across available bacterial and archaeal genomes indicates that the barriers observed in our study are general across the tree of life
The birth of new exons: Mechanisms and evolutionary consequences
No full textABSTRACT A significant amount of literature was dedicated to hypotheses concerning the origin of ancient introns and exons, but accumulating evidence indicates that new exons are also constantly being added to evolving genomes. Several mechanisms contribute to the creation of novel exons in metazoan genomes, including whole gene and single exon duplications, but perhaps the most intriguing are events of exonization, where intronic sequences become exons de novo. Exonizations of intronic sequences, particularly those originating from repetitive elements, are now widely documented in many genomes including human, mouse, dog, and fish. Such de novo appearance of exons is very frequently associated with alternative splicing, with the new exon-containing variant typically being the rare one. This allows the new variant to be evolutionarily tested without compromising the original one, and provides an evolutionary strategy for generation of novel functions with minimum damage to the existing functional repertoire. This review discusses the molecular mechanisms leading to exonization, its extent in vertebrate genomes, and its evolutionary implications
"Simha Rotem (1924-2018): Ad memoriam. The broom and the resilience"
No full textSimha Rotem was born in Warsaw in 1924. He was one of the most important member of the Warsaw
Ghetto uprising in April 1943. Under the cover name of Kazik. He was a leader of the young Jews who were one of the
first in Europe to rebel against the Nazi occupation. His original name is Symon Rathajzer, who upon his arrival in
Israel he changed in Simha Rotem to symbolize a new beginning. His heroic and history is full of anecdotes that
encroach of the unbelievable. Rotem came in and out of the ghetto, through the city’s sewers, besieged and burned, to
bringing news and organizing the escape of the few survivors. Thanks to him the last fighters of the ghetto succeeded in
acriding the “Aryan” area of the city, finding refuge from not Jewish people connected with the Polish resistance. In
1944 Rotem fighted in the Warsaw uprising against the Nazi occupation. He was one of the leader of the Jewish exodus
from Poland to Israel. He contributed to save thousands of people. The author died in Jerusalem in 2018
Non-self RNA sensing in virus infected cells and activation of antiviral immunity
No full textColloque organisé par Jean-Luc Imler (Université de Strasbourg) et Raul Andino (UCSF, USA) du 27 août au 1er septembre 2012 Participants Shizuo Akira, Raul Andino, Bruce Beutler, Stephen Cusack, Ding Shou-Wei, Takashi Fujita, Akira Tajima-Goto, Otto Haller, Jules Hoffmann, Veit Hornung, Jean-Luc Imler, Karim Majzoub, Carine Meignin, Eric Miska, Jan Rehwinkel, Carla Saleh, Rotem Sorek, Volker Thiel, Joao Trindade Marques, Ronald van Rij, Olivier Voinnet, Friedemann Weber -- Abstract Innate imm..
Extensive reshaping of bacterial operons by programmed mRNA decay
No full textBacterial operons synchronize the expression of multiple genes by placing them under the control of a shared promoter. It was previously shown that polycistronic transcripts can undergo differential RNA decay, leaving some genes within the polycistron more stable than others, but the extent of regulation by differential mRNA decay or its evolutionary conservation remains unknown. Here, we find that a substantial fraction of E. coli genes display non-uniform mRNA stoichiometries despite being coded from the same operon. We further show that these altered operon stoichiometries are shaped post-transcriptionally by differential mRNA decay, which is regulated by RNA structures that protect specific regions in the transcript from degradation. These protective RNA structures are generally coded within the protein-coding regions of the regulated genes and are frequently evolutionarily conserved. Furthermore, we provide evidence that differences in ribosome densities across polycistronic transcript segments, together with the conserved structural RNA elements, play a major role in the differential decay process. Our results highlight a major role for differential mRNA decay in shaping bacterial transcriptomes.</div
Optimality and sub-optimality in a bacterial growth law.
No full textOrganisms adjust their gene expression to improve fitness in diverse environments. But finding the optimal expression in each environment presents a challenge. We ask how good cells are at finding such optima by studying the control of carbon catabolism genes in Escherichia coli. Bacteria show a growth law: growth rate on different carbon sources declines linearly with the steady-state expression of carbon catabolic genes. We experimentally modulate gene expression to ask if this growth law always maximizes growth rate, as has been suggested by theory. We find that the growth law is optimal in many conditions, including a range of perturbations to lactose uptake, but provides sub-optimal growth on several other carbon sources. Combining theory and experiment, we genetically re-engineer E. coli to make sub-optimal conditions into optimal ones and vice versa. We conclude that the carbon growth law is not always optimal, but represents a practical heuristic that often works but sometimes fails
Measuring message gossiping in P2P networks and providing incentives in cryptocurrencies
No full textThesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2018.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 47-48).In this thesis, we present Plutus, an efficient and game-theoretically proven incentive mechanism for Algorand, a proof-of-stake cryptocurrency. In order to operate, Algorand requires users to constantly propagate messages but has no mechanism to incentivize users to do so. Plutus solves this problem by keeping track of each message propagation path and rewarding the users who propagated messages using a lottery. We implemented a prototype of Plutus on top of Algorand to measure the performance and overhead of Plutus. Experimental results show that with Plutus, Algorand's block confirmation time increases by only 7% and that there is no penalty on Algorand's scalability.by Rotem Hemo.M. Eng
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