Does phytoestrogen supplementation improve cognition in humans? A systematic review

Abstract

Recent evidence indicates that resveratrol, a phytoestrogen, can improve cognitive function in postmenopausal women by enhancing cerebral vasodilator responsiveness. We examine the effects of phytoestrogen supplementation on cognition and compare resveratrol with other phytoestrogens. Databases were searched for reports of randomized controlled trials (RCTs) containing terms describing phytoestrogens together with terms relating to cognition. Effect sizes were determined for changes in cognition. We identified 23 RCTs, 15 with isoflavone and eight with resveratrol or grape formulations. Six soy isoflavone studies showed positive cognitive effects of medium size. Greater benefits were seen in women who were <10 years postmenopausal and supplemented for <6 months. Small-to-medium effect–size cognitive benefits of resveratrol were seen in four studies of older adults of mixed gender and in postmenopausal women who took 150–200 mg resveratrol daily for at least 14 weeks. No benefits were seen in three studies using red clover or grape formulations. Supplementation with either soy isoflavone or resveratrol improved executive function and memory domains of cognitively normal older adults in half of the included studies, mostly with medium effect sizes. The cognitive benefit of resveratrol was related to improved cerebral perfusion.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2wPDIdv

Issue Information

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2wPq6za

Resveratrol and inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, comprising ulcerative colitis (UC) and Crohn's disease (CD). Progression of IBD leads to long-term impairment of intestinal structure and function. The pathogenesis of IBD is complex, involving environmental, immunological, genetic, microbial, and psychological factors. The conventional therapies and many existing biopharmaceuticals for IBD have limited efficacy or adverse effects. As a promising safe and effective therapy for IBD, resveratrol has been studied widely, as it has shown anti-inflammatory and antioxidant activity. Resveratrol's mechanism of action involves multiple immune responses and signaling pathways; it is absorbed quickly and metabolized into various derivatives. However, the poor water solubility and low bioavailability of resveratrol limit its clinical applications. Further research should attempt to improve the stability and oral bioavailability of resveratrol by modification and various delivery systems.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2wRH0s3

When disaster strikes, will your community be prepared?

If a disaster hits your community, will you be prepared? Are your leaders asking the right questions and taking the right steps to make sure your community could recover quickly and completely? Learn more about the flexible and adaptable resources from NIST's Community Resilience program that will help put your community on the path toward greater resilience.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2hu0GfT

Hopkins Researchers Deliver Blood Samples Using Drone in 161 Mile Journey

The last few weeks have been full of natural disasters striking Mexico, islands in the Caribbean, and the United States mainland. Roads are damaged and entire communities have been cut off from help for days at a time, while the potential for infectious diseases to thrive has skyrocketed. Moreover, patients often end up without their prescription medication and some meds that require refrigeration go bad. In many cases, as with people on insulin, this can be a life threatening problem.

Drones may soon become part of future rescue missions. Researchers at Johns Hopkins University have just demonstrated that they can safely transport blood samples for great distances in a fairly challenging environment. The team used a Latitude Engineering HQ-40 unmanned aerial vehicle with a built-in temperature controlled compartment that takes off and lands vertically. They flew the blood samples above an Arizona desert for up to 161 miles (259 Km) while tracking the payload's temperature, which stayed within the proscribed limits. They then tested the samples for integrity using a series of chemistry and hematology tests.

In summary, their findings showed that the flown blood samples were just as good as those that were intentionally left stored in a temperature controlled case inside a parked car. Actually, since the temperature control system inside the car kept the samples about five degrees warmer than those that flew, their glucose and potassium levels were not as robust as the flown ones.

"We expect that in many cases, drone transport will be the quickest, safest, and most efficient option to deliver some biological samples to a laboratory from rural or urban settings," says Timothy Amukele, assistant professor of pathology at the Johns Hopkins University School of Medicine and the paper's senior author.

Via: Johns Hopkins…

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2fMfM06

Meet the team who ‘woke’ a man from 15 years in vegetative state

Angela Sirigu and her team stimulated the brain of a man who fell into a vegetative state after a car crash 2001. Now he can move his eyes and listen to music

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A single gp120 residue can affect HIV-1 tropism in macaques

by Gregory Q. Del Prete, Brandon F. Keele, Jeannine Fode, Keyur Thumar, Adrienne E. Swanstrom, Anthony Rodriguez, Alice Raymond, Jacob D. Estes, Celia C. LaBranche, David C. Montefiori, Vineet N. KewalRamani, Jeffrey D. Lifson, Paul D. Bieniasz, Theodora Hatziioannou

Species-dependent variation in proteins that aid or limit virus replication determines the ability of lentiviruses to jump between host species. Identifying and overcoming these differences facilitates the development of animal models for HIV-1, including models based on chimeric SIVs that express HIV-1 envelope (Env) glycoproteins, (SHIVs) and simian-tropic HIV-1 (stHIV) strains. Here, we demonstrate that the inherently poor ability of most HIV-1 Env proteins to use macaque CD4 as a receptor is improved during adaptation by virus passage in macaques. We identify a single amino acid, A281, in HIV-1 Env that consistently changes during adaptation in macaques and affects the ability of HIV-1 Env to use macaque CD4. Importantly, mutations at A281 do not markedly affect HIV-1 Env neutralization properties. Our findings should facilitate the design of HIV-1 Env proteins for use in non-human primate models and thus expedite the development of clinically relevant reagents for testing interventions against HIV-1.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2wRX6ls

A single gp120 residue can affect HIV-1 tropism in macaques

by Gregory Q. Del Prete, Brandon F. Keele, Jeannine Fode, Keyur Thumar, Adrienne E. Swanstrom, Anthony Rodriguez, Alice Raymond, Jacob D. Estes, Celia C. LaBranche, David C. Montefiori, Vineet N. KewalRamani, Jeffrey D. Lifson, Paul D. Bieniasz, Theodora Hatziioannou

Species-dependent variation in proteins that aid or limit virus replication determines the ability of lentiviruses to jump between host species. Identifying and overcoming these differences facilitates the development of animal models for HIV-1, including models based on chimeric SIVs that express HIV-1 envelope (Env) glycoproteins, (SHIVs) and simian-tropic HIV-1 (stHIV) strains. Here, we demonstrate that the inherently poor ability of most HIV-1 Env proteins to use macaque CD4 as a receptor is improved during adaptation by virus passage in macaques. We identify a single amino acid, A281, in HIV-1 Env that consistently changes during adaptation in macaques and affects the ability of HIV-1 Env to use macaque CD4. Importantly, mutations at A281 do not markedly affect HIV-1 Env neutralization properties. Our findings should facilitate the design of HIV-1 Env proteins for use in non-human primate models and thus expedite the development of clinically relevant reagents for testing interventions against HIV-1.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2wRX6ls

Anthrax edema toxin disrupts distinct steps in Rab11-dependent junctional transport

by Annabel Guichard, Prashant Jain, Mahtab Moayeri, Ruth Schwartz, Stephen Chin, Lin Zhu, Beatriz Cruz-Moreno, Janet Z. Liu, Bernice Aguilar, Andrew Hollands, Stephen H. Leppla, Victor Nizet, Ethan Bier

Various bacterial toxins circumvent host defenses through overproduction of cAMP. In a previous study, we showed that edema factor (EF), an adenylate cyclase from Bacillus anthracis, disrupts endocytic recycling mediated by the small GTPase Rab11. As a result, cargo proteins such as cadherins fail to reach inter-cellular junctions. In the present study, we provide further mechanistic dissection of Rab11 inhibition by EF using a combination of Drosophila and mammalian systems. EF blocks Rab11 trafficking after the GTP-loading step, preventing a constitutively active form of Rab11 from delivering cargo vesicles to the plasma membrane. Both of the primary cAMP effector pathways -PKA and Epac/Rap1- contribute to inhibition of Rab11-mediated trafficking, but act at distinct steps of the delivery process. PKA acts early, preventing Rab11 from associating with its effectors Rip11 and Sec15. In contrast, Epac functions subsequently via the small GTPase Rap1 to block fusion of recycling endosomes with the plasma membrane, and appears to be the primary effector of EF toxicity in this process. Similarly, experiments conducted in mammalian systems reveal that Epac, but not PKA, mediates the activity of EF both in cell culture and in vivo. The small GTPase Arf6, which initiates endocytic retrieval of cell adhesion components, also contributes to junctional homeostasis by counteracting Rab11-dependent delivery of cargo proteins at sites of cell-cell contact. These studies have potentially significant practical implications, since chemical inhibition of either Arf6 or Epac blocks the effect of EF in cell culture and in vivo, opening new potential therapeutic avenues for treating symptoms caused by cAMP-inducing toxins or related barrier-disrupting pathologies.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2yCIvMH

Correction: Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization

by Cecilia Rademeyer, Bette Korber, Michael S. Seaman, Elena E. Giorgi, Ruwayhida Thebus, Alexander Robles, Daniel J. Sheward, Kshitij Wagh, Jetta Garrity, Brittany R. Carey, Hongmei Gao, Kelli M. Greene, Haili Tang, Gama P. Bandawe, Jinny C. Marais, Thabo E. Diphoko, Peter Hraber, Nancy Tumba, Penny L. Moore, Glenda E. Gray, James Kublin, M. Juliana McElrath, Marion Vermeulen, Keren Middelkoop, Linda-Gail Bekker, Michael Hoelscher, Leonard Maboko, Joseph Makhema, Merlin L. Robb, Salim Abdool Karim, Quarraisha Abdool Karim, Jerome H. Kim, Beatrice H. Hahn, Feng Gao, Ronald Swanstrom, Lynn Morris, David C. Montefiori, Carolyn Williamson

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2yEbmjQ

A single gp120 residue can affect HIV-1 tropism in macaques

by Gregory Q. Del Prete, Brandon F. Keele, Jeannine Fode, Keyur Thumar, Adrienne E. Swanstrom, Anthony Rodriguez, Alice Raymond, Jacob D. Estes, Celia C. LaBranche, David C. Montefiori, Vineet N. KewalRamani, Jeffrey D. Lifson, Paul D. Bieniasz, Theodora Hatziioannou

Species-dependent variation in proteins that aid or limit virus replication determines the ability of lentiviruses to jump between host species. Identifying and overcoming these differences facilitates the development of animal models for HIV-1, including models based on chimeric SIVs that express HIV-1 envelope (Env) glycoproteins, (SHIVs) and simian-tropic HIV-1 (stHIV) strains. Here, we demonstrate that the inherently poor ability of most HIV-1 Env proteins to use macaque CD4 as a receptor is improved during adaptation by virus passage in macaques. We identify a single amino acid, A281, in HIV-1 Env that consistently changes during adaptation in macaques and affects the ability of HIV-1 Env to use macaque CD4. Importantly, mutations at A281 do not markedly affect HIV-1 Env neutralization properties. Our findings should facilitate the design of HIV-1 Env proteins for use in non-human primate models and thus expedite the development of clinically relevant reagents for testing interventions against HIV-1.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2wRX6ls

HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways

by Fang Guo, Qiong Zhao, Muhammad Sheraz, Junjun Cheng, Yonghe Qi, Qing Su, Andrea Cuconati, Lai Wei, Yanming Du, Wenhui Li, Jinhong Chang, Ju-Tao Guo

Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) and sulfamoylbenzamides (SBAs), have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or "empty" capsids devoid of pre-genomic RNA and viral DNA polymerase. Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc) DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm. Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids. Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly. Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2wOJSuw

Correction: Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization

by Cecilia Rademeyer, Bette Korber, Michael S. Seaman, Elena E. Giorgi, Ruwayhida Thebus, Alexander Robles, Daniel J. Sheward, Kshitij Wagh, Jetta Garrity, Brittany R. Carey, Hongmei Gao, Kelli M. Greene, Haili Tang, Gama P. Bandawe, Jinny C. Marais, Thabo E. Diphoko, Peter Hraber, Nancy Tumba, Penny L. Moore, Glenda E. Gray, James Kublin, M. Juliana McElrath, Marion Vermeulen, Keren Middelkoop, Linda-Gail Bekker, Michael Hoelscher, Leonard Maboko, Joseph Makhema, Merlin L. Robb, Salim Abdool Karim, Quarraisha Abdool Karim, Jerome H. Kim, Beatrice H. Hahn, Feng Gao, Ronald Swanstrom, Lynn Morris, David C. Montefiori, Carolyn Williamson

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2yEbmjQ

Anthrax edema toxin disrupts distinct steps in Rab11-dependent junctional transport

by Annabel Guichard, Prashant Jain, Mahtab Moayeri, Ruth Schwartz, Stephen Chin, Lin Zhu, Beatriz Cruz-Moreno, Janet Z. Liu, Bernice Aguilar, Andrew Hollands, Stephen H. Leppla, Victor Nizet, Ethan Bier

Various bacterial toxins circumvent host defenses through overproduction of cAMP. In a previous study, we showed that edema factor (EF), an adenylate cyclase from Bacillus anthracis, disrupts endocytic recycling mediated by the small GTPase Rab11. As a result, cargo proteins such as cadherins fail to reach inter-cellular junctions. In the present study, we provide further mechanistic dissection of Rab11 inhibition by EF using a combination of Drosophila and mammalian systems. EF blocks Rab11 trafficking after the GTP-loading step, preventing a constitutively active form of Rab11 from delivering cargo vesicles to the plasma membrane. Both of the primary cAMP effector pathways -PKA and Epac/Rap1- contribute to inhibition of Rab11-mediated trafficking, but act at distinct steps of the delivery process. PKA acts early, preventing Rab11 from associating with its effectors Rip11 and Sec15. In contrast, Epac functions subsequently via the small GTPase Rap1 to block fusion of recycling endosomes with the plasma membrane, and appears to be the primary effector of EF toxicity in this process. Similarly, experiments conducted in mammalian systems reveal that Epac, but not PKA, mediates the activity of EF both in cell culture and in vivo. The small GTPase Arf6, which initiates endocytic retrieval of cell adhesion components, also contributes to junctional homeostasis by counteracting Rab11-dependent delivery of cargo proteins at sites of cell-cell contact. These studies have potentially significant practical implications, since chemical inhibition of either Arf6 or Epac blocks the effect of EF in cell culture and in vivo, opening new potential therapeutic avenues for treating symptoms caused by cAMP-inducing toxins or related barrier-disrupting pathologies.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2yCIvMH

HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways

by Fang Guo, Qiong Zhao, Muhammad Sheraz, Junjun Cheng, Yonghe Qi, Qing Su, Andrea Cuconati, Lai Wei, Yanming Du, Wenhui Li, Jinhong Chang, Ju-Tao Guo

Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) and sulfamoylbenzamides (SBAs), have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or "empty" capsids devoid of pre-genomic RNA and viral DNA polymerase. Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc) DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm. Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids. Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly. Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2wOJSuw

HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways

by Fang Guo, Qiong Zhao, Muhammad Sheraz, Junjun Cheng, Yonghe Qi, Qing Su, Andrea Cuconati, Lai Wei, Yanming Du, Wenhui Li, Jinhong Chang, Ju-Tao Guo

Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) and sulfamoylbenzamides (SBAs), have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or "empty" capsids devoid of pre-genomic RNA and viral DNA polymerase. Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc) DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm. Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids. Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly. Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2wOJSuw

Correction: Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization

by Cecilia Rademeyer, Bette Korber, Michael S. Seaman, Elena E. Giorgi, Ruwayhida Thebus, Alexander Robles, Daniel J. Sheward, Kshitij Wagh, Jetta Garrity, Brittany R. Carey, Hongmei Gao, Kelli M. Greene, Haili Tang, Gama P. Bandawe, Jinny C. Marais, Thabo E. Diphoko, Peter Hraber, Nancy Tumba, Penny L. Moore, Glenda E. Gray, James Kublin, M. Juliana McElrath, Marion Vermeulen, Keren Middelkoop, Linda-Gail Bekker, Michael Hoelscher, Leonard Maboko, Joseph Makhema, Merlin L. Robb, Salim Abdool Karim, Quarraisha Abdool Karim, Jerome H. Kim, Beatrice H. Hahn, Feng Gao, Ronald Swanstrom, Lynn Morris, David C. Montefiori, Carolyn Williamson

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2yEbmjQ

Anthrax edema toxin disrupts distinct steps in Rab11-dependent junctional transport

by Annabel Guichard, Prashant Jain, Mahtab Moayeri, Ruth Schwartz, Stephen Chin, Lin Zhu, Beatriz Cruz-Moreno, Janet Z. Liu, Bernice Aguilar, Andrew Hollands, Stephen H. Leppla, Victor Nizet, Ethan Bier

Various bacterial toxins circumvent host defenses through overproduction of cAMP. In a previous study, we showed that edema factor (EF), an adenylate cyclase from Bacillus anthracis, disrupts endocytic recycling mediated by the small GTPase Rab11. As a result, cargo proteins such as cadherins fail to reach inter-cellular junctions. In the present study, we provide further mechanistic dissection of Rab11 inhibition by EF using a combination of Drosophila and mammalian systems. EF blocks Rab11 trafficking after the GTP-loading step, preventing a constitutively active form of Rab11 from delivering cargo vesicles to the plasma membrane. Both of the primary cAMP effector pathways -PKA and Epac/Rap1- contribute to inhibition of Rab11-mediated trafficking, but act at distinct steps of the delivery process. PKA acts early, preventing Rab11 from associating with its effectors Rip11 and Sec15. In contrast, Epac functions subsequently via the small GTPase Rap1 to block fusion of recycling endosomes with the plasma membrane, and appears to be the primary effector of EF toxicity in this process. Similarly, experiments conducted in mammalian systems reveal that Epac, but not PKA, mediates the activity of EF both in cell culture and in vivo. The small GTPase Arf6, which initiates endocytic retrieval of cell adhesion components, also contributes to junctional homeostasis by counteracting Rab11-dependent delivery of cargo proteins at sites of cell-cell contact. These studies have potentially significant practical implications, since chemical inhibition of either Arf6 or Epac blocks the effect of EF in cell culture and in vivo, opening new potential therapeutic avenues for treating symptoms caused by cAMP-inducing toxins or related barrier-disrupting pathologies.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2yCIvMH

Rapid functional analysis of computationally complex rare human IRF6 gene variants using a novel zebrafish model

by Edward B. Li, Dawn Truong, Shawn A. Hallett, Kusumika Mukherjee, Brian C. Schutte, Eric C. Liao

Large-scale sequencing efforts have captured a rapidly growing catalogue of genetic variations. However, the accurate establishment of gene variant pathogenicity remains a central challenge in translating personal genomics information to clinical decisions. Interferon Regulatory Factor 6 (IRF6) gene variants are significant genetic contributors to orofacial clefts. Although approximately three hundred IRF6 gene variants have been documented, their effects on protein functions remain difficult to interpret. Here, we demonstrate the protein functions of human IRF6 missense gene variants could be rapidly assessed in detail by their abilities to rescue the irf6 ^-/- phenotype in zebrafish through variant mRNA microinjections at the one-cell stage. The results revealed many missense variants previously predicted by traditional statistical and computational tools to be loss-of-function and pathogenic retained partial or full protein function and rescued the zebrafish irf6 ^-/- periderm rupture phenotype. Through mRNA dosage titration and analysis of the Exome Aggregation Consortium (ExAC) database, IRF6 missense variants were grouped by their abilities to rescue at various dosages into three functional categories: wild type function, reduced function, and complete loss-of-function. This sensitive and specific biological assay was able to address the nuanced functional significances of IRF6 missense gene variants and overcome many limitations faced by current statistical and computational tools in assigning variant protein function and pathogenicity. Furthermore, it unlocked the possibility for characterizing yet undiscovered human IRF6 missense gene variants from orofacial cleft patients, and illustrated a generalizable functional genomics paradigm in personalized medicine.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2wOJMmE

Genetic plasticity of the Shigella virulence plasmid is mediated by intra- and inter-molecular events between insertion sequences

by Giulia Pilla, Gareth McVicker, Christoph M. Tang

Acquisition of a single copy, large virulence plasmid, pINV, led to the emergence of Shigella spp. from Escherichia coli. The plasmid encodes a Type III secretion system (T3SS) on a 30 kb pathogenicity island (PAI), and is maintained in a bacterial population through a series of toxin:antitoxin (TA) systems which mediate post-segregational killing (PSK). The T3SS imposes a significant cost on the bacterium, and strains which have lost the plasmid and/or genes encoding the T3SS grow faster than wild-type strains in the laboratory, and fail to bind the indicator dye Congo Red (CR). Our aim was to define the molecular events in Shigella flexneri that cause loss of Type III secretion (T3S), and to examine whether TA systems exert positional effects on pINV. During growth at 37°C, we found that deletions of regions of the plasmid including the PAI lead to the emergence of CR-negative colonies; deletions occur through intra-molecular recombination events between insertion sequences (ISs) flanking the PAI. Furthermore, by repositioning MvpAT (which belongs to the VapBC family of TA systems) near the PAI, we demonstrate that the location of this TA system alters the rearrangements that lead to loss of T3S, indicating that MvpAT acts both globally (by reducing loss of pINV through PSK) as well as locally (by preventing loss of adjacent sequences). During growth at environmental temperatures, we show for the first time that pINV spontaneously integrates into different sites in the chromosome, and this is mediated by inter-molecular events involving IS1294. Integration leads to reduced PAI gene expression and impaired secretion through the T3SS, while excision of pINV from the chromosome restores T3SS function. Therefore, pINV integration provides a reversible mechanism for Shigella to circumvent the metabolic burden imposed by pINV. Intra- and inter-molecular events between ISs, which are abundant in Shigella spp., mediate plasticity of S. flexneri pINV.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2yC9wzW

Genome diversity of marine phages recovered from Mediterranean metagenomes: Size matters

by Mario López-Pérez, Jose M. Haro-Moreno, Rafael Gonzalez-Serrano, Marcos Parras-Moltó, Francisco Rodriguez-Valera

Marine viruses play a critical role not only in the global geochemical cycles but also in the biology and evolution of their hosts. Despite their importance, viral diversity remains underexplored mostly due to sampling and cultivation challenges. Direct sequencing approaches such as viromics has provided new insights into the marine viral world. As a complementary approach, we analysed 24 microbial metagenomes (>0.2 μm size range) obtained from six sites in the Mediterranean Sea that vary by depth, season and filter used to retrieve the fraction. Filter-size comparison showed a significant number of viral sequences that were retained on the larger-pore filters and were different from those found in the viral fraction from the same sample, indicating that some important viral information is missing using only assembly from viromes. Besides, we were able to describe 1,323 viral genomic fragments that were more than 10Kb in length, of which 36 represented complete viral genomes including some of them retrieved from a cross-assembly from different metagenomes. Host prediction based on sequence methods revealed new phage groups belonging to marine prokaryotes like SAR11, Cyanobacteria or SAR116. We also identified the first complete virophage from deep seawater and a new endemic clade of the recently discovered Marine group II Euryarchaeota virus. Furthermore, analysis of viral distribution using metagenomes and viromes indicated that most of the new phages were found exclusively in the Mediterranean Sea and some of them, mostly the ones recovered from deep metagenomes, do not recruit in any database probably indicating higher variability and endemicity in Mediterranean bathypelagic waters. Together these data provide the first detailed picture of genomic diversity, spatial and depth variations of viral communities within the Mediterranean Sea using metagenome assembly.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2wOJKew

p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis

by Francesco Napoletano, Benjamin Gibert, Keren Yacobi-Sharon, Stéphane Vincent, Clémentine Favrot, Patrick Mehlen, Victor Girard, Margaux Teil, Gilles Chatelain, Ludivine Walter, Eli Arama, Bertrand Mollereau

The importance of regulated necrosis in pathologies such as cerebral stroke and myocardial infarction is now fully recognized. However, the physiological relevance of regulated necrosis remains unclear. Here, we report a conserved role for p53 in regulating necrosis in Drosophila and mammalian spermatogenesis. We found that Drosophila p53 is required for the programmed necrosis that occurs spontaneously in mitotic germ cells during spermatogenesis. This form of necrosis involved an atypical function of the initiator caspase Dronc/Caspase 9, independent of its catalytic activity. Prevention of p53-dependent necrosis resulted in testicular hyperplasia, which was reversed by restoring necrosis in spermatogonia. In mouse testes, p53 was required for heat-induced germ cell necrosis, indicating that regulation of necrosis is a primordial function of p53 conserved from invertebrates to vertebrates. Drosophila and mouse spermatogenesis will thus be useful models to identify inducers of necrosis to treat cancers that are refractory to apoptosis.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2yCoxl5

The bacterial Sec system is required for the organization and function of the MreB cytoskeleton

by Sutharsan Govindarajan, Orna Amster-Choder

The Sec system is responsible for protein insertion, translocation and secretion across membranes in all cells. The bacterial actin homolog MreB controls various processes, including cell wall synthesis, membrane organization and polarity establishment. Here we show that the two systems genetically interact and that components of the Sec system, especially the SecA motor protein, are essential for spatiotemporal organization of MreB in E. coli, as evidenced by the accumulation of MreB at irregular sites in Sec-impaired cells. MreB mislocalization in SecA-defective cells significantly affects MreB-coordinated processes, such as cell wall synthesis, and induce formation of membrane invaginations enriched in high fluidity domains. Additionally, MreB is not recruited to the FtsZ ring in secA mutant cells, contributing to division arrest and cell filamentation. Our results show that all these faults are due to improper targeting of MreB to the membrane in the absence of SecA. Thus, when we reroute RodZ, MreB membrane-anchor, by fusing it to a SecA-independent integral membrane protein and overproducing it, MreB localization is restored and the defect in cell division is corrected. Notably, the RodZ moiety is not properly inserted into the membrane, strongly suggesting that it only serves as a bait for placing MreB around the cell circumference. Finally, we show that MreB localization depends on SecA also in C. crescentus, suggesting that regulation of MreB by the Sec system is conserved in bacteria. Taken together, our data reveal that the secretion system plays an important role in determining the organization and functioning of the cytoskeletal system in bacteria.

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Formation of a TBX20-CASZ1 protein complex is protective against dilated cardiomyopathy and critical for cardiac homeostasis

by Leslie Kennedy, Erin Kaltenbrun, Todd M. Greco, Brenda Temple, Laura E. Herring, Ileana M. Cristea, Frank L. Conlon

By the age of 40, one in five adults without symptoms of cardiovascular disease are at risk for developing congestive heart failure. Within this population, dilated cardiomyopathy (DCM) remains one of the leading causes of disease and death, with nearly half of cases genetically determined. Though genetic and high throughput sequencing-based approaches have identified sporadic and inherited mutations in a multitude of genes implicated in cardiomyopathy, how combinations of asymptomatic mutations lead to cardiac failure remains a mystery. Since a number of studies have implicated mutations of the transcription factor TBX20 in congenital heart diseases, we investigated the underlying mechanisms, using an unbiased systems-based screen to identify novel, cardiac-specific binding partners. We demonstrated that TBX20 physically and genetically interacts with the essential transcription factor CASZ1. This interaction is required for survival, as mice heterozygous for both Tbx20 and Casz1 die post-natally as a result of DCM. A Tbx20 mutation associated with human familial DCM sterically interferes with the TBX20-CASZ1 interaction and provides a physical basis for how this human mutation disrupts normal cardiac function. Finally, we employed quantitative proteomic analyses to define the molecular pathways mis-regulated upon disruption of this novel complex. Collectively, our proteomic, biochemical, genetic, and structural studies suggest that the physical interaction between TBX20 and CASZ1 is required for cardiac homeostasis, and further, that reduction or loss of this critical interaction leads to DCM. This work provides strong evidence that DCM can be inherited through a digenic mechanism.

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A two-step transport pathway allows the mother cell to nurture the developing spore in Bacillus subtilis

by Fernando H. Ramírez-Guadiana, Alexander J. Meeske, Christopher D. A. Rodrigues, Rocío del Carmen Barajas-Ornelas, Andrew C. Kruse, David Z. Rudner

One of the hallmarks of bacterial endospore formation is the accumulation of high concentrations of pyridine-2,6-dicarboxylic acid (dipicolinic acid or DPA) in the developing spore. This small molecule comprises 5–15% of the dry weight of dormant spores and plays a central role in resistance to both wet heat and desiccation. DPA is synthesized in the mother cell at a late stage in sporulation and must be translocated across two membranes (the inner and outer forespore membranes) that separate the mother cell and forespore. The enzymes that synthesize DPA and the proteins required to translocate it across the inner forespore membrane were identified over two decades ago but the factors that transport DPA across the outer forespore membrane have remained mysterious. Here, we report that SpoVV (formerly YlbJ) is the missing DPA transporter. SpoVV is produced in the mother cell during the morphological process of engulfment and specifically localizes in the outer forespore membrane. Sporulating cells lacking SpoVV produce spores with low levels of DPA and cells engineered to express SpoVV and the DPA synthase during vegetative growth accumulate high levels of DPA in the culture medium. SpoVV resembles concentrative nucleoside transporters and mutagenesis of residues predicted to form the substrate-binding pocket supports the idea that SpoVV has a similar structure and could therefore function similarly. These findings provide a simple two-step transport mechanism by which the mother cell nurtures the developing spore. DPA produced in the mother cell is first translocated into the intermembrane space by SpoVV and is then imported into the forespore by the SpoVA complex. This pathway is likely to be broadly conserved as DPA synthase, SpoVV, and SpoVA proteins can be found in virtually all endospore forming bacteria.

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Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data

by Niedzica Camacho, Peter Van Loo, Sandra Edwards, Jonathan D. Kay, Lucy Matthews, Kerstin Haase, Jeremy Clark, Nening Dennis, Sarah Thomas, Barbara Kremeyer, Jorge Zamora, Adam P. Butler, Gunes Gundem, Sue Merson, Hayley Luxton, Steve Hawkins, Mohammed Ghori, Luke Marsden, Adam Lambert, Katalin Karaszi, Gill Pelvender, Charlie E. Massie, ZSofia Kote-Jarai, Keiran Raine, David Jones, William J. Howat, Steven Hazell, Naomi Livni, Cyril Fisher, Christopher Ogden, Pardeep Kumar, Alan Thompson, David Nicol, Erik Mayer, Tim Dudderidge, Yongwei Yu, Hongwei Zhang, Nimish C. Shah, Vincent J. Gnanapragasam, The CRUK-ICGC Prostate Group , William Isaacs, Tapio Visakorpi, Freddie Hamdy, Dan Berney, Clare Verrill, Anne Y. Warren, David C. Wedge, Andrew G. Lynch, Christopher S. Foster, Yong Jie Lu, G. Steven Bova, Hayley C. Whitaker, Ultan McDermott, David E. Neal, Rosalind Eeles, Colin S. Cooper, Daniel S. Brewer

A variety of models have been proposed to explain regions of recurrent somatic copy number alteration (SCNA) in human cancer. Our study employs Whole Genome DNA Sequence (WGS) data from tumor samples (n = 103) to comprehensively assess the role of the Knudson two hit genetic model in SCNA generation in prostate cancer. 64 recurrent regions of loss and gain were detected, of which 28 were novel, including regions of loss with more than 15% frequency at Chr4p15.2-p15.1 (15.53%), Chr6q27 (16.50%) and Chr18q12.3 (17.48%). Comprehensive mutation screens of genes, lincRNA encoding sequences, control regions and conserved domains within SCNAs demonstrated that a two-hit genetic model was supported in only a minor proportion of recurrent SCNA losses examined (15/40). We found that recurrent breakpoints and regions of inversion often occur within Knudson model SCNAs, leading to the identification of ZNF292 as a target gene for the deletion at 6q14.3-q15 and NKX3.1 as a two-hit target at 8p21.3-p21.2. The importance of alterations of lincRNA sequences was illustrated by the identification of a novel mutational hotspot at the KCCAT42, FENDRR, CAT1886 and STCAT2 loci at the 16q23.1-q24.3 loss. Our data confirm that the burden of SCNAs is predictive of biochemical recurrence, define nine individual regions that are associated with relapse, and highlight the possible importance of ion channel and G-protein coupled-receptor (GPCR) pathways in cancer development. We concluded that a two-hit genetic model accounts for about one third of SCNA indicating that mechanisms, such haploinsufficiency and epigenetic inactivation, account for the remaining SCNA losses.

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Correction: Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused by CLDN19 gene mutations

Yamaguti PM, Neves FDAR, Hotton D, et al. Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused by CLDN19 gene mutations. J Med Genet 2017;54:26–37.

One of the author names is spelled incorrectly. 'Pascal Houiller' should be 'Pascal Houillier'.

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Exercise and pregnancy in recreational and elite athletes: 2016/17 evidence summary from the IOC expert group meeting, Lausanne. Part 4--Recommendations for future research

Background

This is Part 4 in the series of reviews from the International Olympic Committee (IOC) expert committee on exercise and pregnancy in recreational and elite athletes. Part 1 focused on the effects of training during pregnancy and on the management of common pregnancy-related complaints experienced by athletes;1 Part 2 addressed maternal and foetal perinatal outcomes;2 Part 3 reviewed the implications of pregnancy and childbirth on return to exercise and on common illnesses and complaints in the postpartum period.3 Parts 1–3 are all open access papers.

In Part 4, we recommend future research based on Parts 1–3. The systematic reviews, on which the previous Parts were based, revealed many gaps in knowledge relating to strenuous exercise during pregnancy and in the postpartum period, in both regular recreational exercisers and elite athletes. Important research questions are listed below, in relation to the foci of Parts 1–3,...

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Remediation and rehabilitation programmes for health professionals: challenges for the future

'To improve is to change; to be perfect is to change often.'

—Winston Churchill

Health professions regulatory authorities are responsible for assessing the clinical performance of healthcare professionals.1 2 Some of them also have the responsibility for programming remediation interventions for health professionals with deficits in clinical performance.2 3 Available data on medical errors, malpractice claims, disciplinary actions and various other sources suggest that between 6% and 12% of physicians meet criteria for 'dyscompetence' in the USA.4 5 Elsewhere, the percentage varies according to the data sources.6 In Ontario, for instance, where the data come from randomly selected physicians, it is estimated that approximately 15% of family physicians and 3% of specialists have considerable deficiencies.4 7 8 Performance problems can have an impact on quality of care and patient safety.5...

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Comparison of control charts for monitoring clinical performance using binary data

Background

Time series charts are increasingly used by clinical teams to monitor their performance, but statistical control charts are not widely used, partly due to uncertainty about which chart to use. Although there is a large literature on methods, there are few systematic comparisons of charts for detecting changes in rates of binary clinical performance data.

Methods

We compared four control charts for binary data: the Shewhart p-chart; the exponentially weighted moving average (EWMA) chart; the cumulative sum (CUSUM) chart; and the g-chart. Charts were set up to have the same long-term false signal rate. Chart performance was then judged according to the expected number of patients treated until a change in rate was detected.

Results

For large absolute increases in rates (>10%), the Shewhart p-chart and EWMA both had good performance, although not quite as good as the CUSUM. For small absolute increases (<10%), the CUSUM detected changes more rapidly. The g-chart is designed to efficiently detect decreases in low event rates, but it again had less good performance than the CUSUM.

Implications

The Shewhart p-chart is the simplest chart to implement and interpret, and performs well for detecting large changes, which may be useful for monitoring processes of care. The g-chart is a useful complement for determining the success of initiatives to reduce low-event rates (eg, adverse events). The CUSUM may be particularly useful for faster detection of problems with patient safety leading to increases in adverse event rates.  

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Expansion behaviour of a binary solid-liquid fluidised bed with different solid mass ratio

Publication date: Available online 25 September 2017
Source:Advanced Powder Technology
Author(s): Md. Shakhaoath Khan, Geoffrey M. Evans, Zhengbiao Peng, Elham Doroodchi, Behdad Moghtaderi, Jyeshtharaj B. Joshi, Subhasish Mitra
This study reports the effect of particle mass compositions on the bed expansion behaviour of a binary solid liquid fluidised bed (SLFB) system. Experiments were performed comprising equal density (2230kgm⁻³) spherical glass beads particles of diameter 3, 5 and 8mm and water as fluidising medium with different particle mass ratios varying from 0.17 to 6.0. In the expanded bed, both segregated and intermixed zones were observed depending on the different particle diameter combinations. In a completely segregated SLFB, the bottom monosized layer exhibited a negative deviation ∼23% whereas a positive deviation ∼25% was found in the top monosized layer when compared with the corresponding pure monosized system. A small mixing zone spanning approximately two particle diameters thick was observed to exist even in a completely segregated SLFB for higher diameter ratio cases. A slight decrease in the mixing zone height was noted with increasing liquid superficial velocity. For lower diameter ratio cases, a relatively lager mixing zone height was observed which increased with increasing liquid superficial velocity. The bed expansion ratio was noted to decrease with increasing solid mass ratio however it increased with increase in the fluidising velocity ratio following a reasonable power law trend. The expanded bed height of the binary mixture was not entirely additive of its corresponding mono-component bed heights and both positive and negative deviations were observed. Finally, a two-dimensional (2D) Eulerian-Eulerian (E-E) model incorporating the kinetic theory of granular flow (KTGF) was used to quantify the binary system hydrodynamics. The model predicted expanded bed height agreed with experimental measurements within ±6% deviation. Presence of a mixing zone was also confirmed by the CFD model and simulated particle phase volume fraction distribution qualitatively agreed with the experimental visualisations.

Graphical abstract

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Mutations de PNPLA1 dans les ichtyoses congénitales autosomiques récessives

Publication date: Available online 25 September 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): O. Dereure




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Have you hugged your product manager lately?

"When someone is compelled to come up and hug you at the Farmer's Market because you work on MindManager, you know there's something special about this product."

This is what Michael Deutch, MindManager's VP of Product Management, shared with me during my first week here at Corel, which acquired MindManager in August 2016.

Michael's an interesting guy. Besides being a yogi, a vegan and living by the beach, he's unlike many project managers in that he's not so focused in on product features that he forgets the real value that his product brings to people's day to day lives. And I suppose that's also why he's been working with MindManager for more than a decade. He truly loves this software and can't imagine managing his work, and life, without it.  

So, here's my confession: I'd never heard of MindManager until I was recruited to join this (brilliant) marketing team. But now I am a total convert. Mapping is really therapeutic. I mean it … actually therapeutic.

Think about the last time you wrote a "to-do" list. For me, it's something I tend to do at the end of the day to help myself "close off." More recently, I've heard this described as "mental load" … that it's a burden on our brains when we carry around so many bits of information and tasks to remember. It's exhausting, and ultimately this kind of burden impacts our ability to be creative or even think strategically.

Here's an example of how mapping eases this burden by providing a single locale for all information — at both a high-level and a granular level. In this example, everyone on this project team knows that everything they need is right here in this one spot … no more hunting through email chains or intranet docs!

 

My colleagues in Germany like to refer to MindManager as the "swiss army knife" of business. Not only is it a great metaphor, but it's incredibly accurate because, as I've learned more recently, there is literally nothing — nothing! — that cannot be mapped. And who doesn't want a map to help them get where they're going?

Over the next little while, I'm looking forward to sharing some of the many applications for mind mapping here on this blog. And if you'd like to share yours, that would be even better!  

Now go on … find a product manager in your company and give them a big ol' hug!  

 

About the author: Julie Harrison joined Corel this past July as Senior Manager, MindManager Global Marketing. In her role, she'll be focusing on content and campaigns for regions worldwide, since MindManager is currently in use by millions of people in thousands of global companies. She can be reached at  julie [dot] harrison [at] corel [dot] com.  

The post Have you hugged your product manager lately? appeared first on Mindjet Blog.

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Synapse-specific astrocyte gating of amygdala-related behavior

Synapse-specific astrocyte gating of amygdala-related behavior

Nature Neuroscience, Published online: 25 September 2017; doi:10.1038/nn.4649

Astrocytes differentially regulate excitatory and inhibitory synaptic transmission in the CeM, the major output nucleus of the amygdala. Astrocytes thereby reduce neuronal activity in the CeM and diminish fear expression in vivo. Therefore, astrocytes influence neural network activity and animal behavior through the regulation of specific synapses.

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α-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B

α-synuclein interacts with PrP^C to induce cognitive impairment through mGluR5 and NMDAR2B

Nature Neuroscience, Published online: 25 September 2017; doi:10.1038/nn.4648

The precise underpinnings of Parkinson's disease and other disorders associated with the accumulation of α-synuclein are unclear. This study shows that PrP^C mediates α-synuclein-associated synaptic dysfunction and memory deficits. Blocking specific events in receptor biology rescued cognitive deficits in mice, suggesting new possibilities for intervention in synucleinopathies.

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Astrocytes control synaptic strength by two distinct v-SNARE-dependent release pathways

Astrocytes control synaptic strength by two distinct v-SNARE-dependent release pathways

Nature Neuroscience, Published online: 25 September 2017; doi:10.1038/nn.4647

The mechanisms of gliotransmitter release and their impact on neuronal signaling have remained largely elusive. The authors describe two functionally non-overlapping v-SNARE-dependent astrocytic release pathways that oppositely control synaptic strength at presynaptic sites. Thus, astrocytes are able to fine-tune fast glutamatergic neurotransmission and control fundamental processes of synaptic communication.

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Macromolecular Antiviral Agents against Zika, Ebola, SARS, and Other Pathogenic Viruses

Abstract

Viral pathogens continue to constitute a heavy burden on healthcare and socioeconomic systems. Efforts to create antiviral drugs repeatedly lag behind the advent of pathogens and growing understanding is that broad-spectrum antiviral agents will make strongest impact in future antiviral efforts. This work performs selection of synthetic polymers as novel broadly active agents and demonstrates activity of these polymers against Zika, Ebola, Lassa, Lyssa, Rabies, Marburg, Ebola, influenza, herpes simplex, and human immunodeficiency viruses. Results presented herein offer structure–activity relationships for these pathogens in terms of their susceptibility to inhibition by polymers, and for polymers in terms of their anionic charge and hydrophobicity that make up broad-spectrum antiviral agents. The identified leads cannot be predicted based on prior data on polymer-based antivirals and represent promising candidates for further development as preventive microbicides.

Broad spectrum antiviral agents are designed through systematic variation of the polymer composition, specifically the nature of the anionic charge of the polymer and hydrophobicity of the backbone. Structure–function relationship reveals unexpected lead candidates with inhibitory antiviral activity against all tested enveloped viruses.

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