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10.1126/science.1211204
122,270,322
The 3.5 angstrom–resolution structure provides insights into the architecture of the eukaryotic ribosome and its regulation.
10.1038/nrmicro3155
The structures of eukaryotic ribosomes reported in this work and in references 124–126 open the way to investigating the specificity of antibiotic interactions with the ribosome, as well as the development of anticancer drugs.
10.1073/pnas.1416515111
103,367,486
Significance The Crumbs–PALS1–PATJ complex is vital for the development and maintenance of the polarity of diverse tissues. Defects in Crumbs–PALS1–PATJ complex formation are known to cause diseases such as cancer and blindness. The highly conserved cytoplasmic tail of the transmembrane protein Crumbs is responsible fo...
10.1038/nrn.2016.18
This paper shows that the MPP5 PSG forms an integral structural unit in binding to CRB-CT. A structural analysis indicates that the ligand-binding induced domain-swapped homodimer formation of MPP5 PSG may represent a general mode for MAGUKs in organizing large protein complexes in synapses.
10.1042/bj20130783
39,752,953
PDZ domains are highly abundant protein–protein interaction modules and are often found in multidomain scaffold proteins. PDZ-domain-containing scaffold proteins regulate multiple biological processes, including trafficking and clustering receptors and ion channels at defined membrane regions, organizing and targeting ...
10.1038/nrn.2016.18
This review comprehensively summarizes the mechanistic bases of complex formation between the extended PDZ domain and the extended PBM, as well as the regulated PDZ–target interactions.
10.1152/jn.1991.65.2.188
122,651,498
1. Single-unit activity in the cingulate cortex of the monkey was recorded during the performance of sensorially (visual, auditory, or tactile) triggered or self-paced forelimb key press movements. 2. Microelectrodes were inserted into the broad rostrocaudal expanse of the cingulate cortex, including the upper and lowe...
10.1038/nrn1704
This study provides the neurophysiological characterization of the two cingulate motor areas. These motor areas are key outputs from the cingulate gyrus for mediating skeletomotor functions, they are pivotal to the subregional differentiation of the MCC into two parts, and they suggest that there are different mechanis...
10.1126/science.107587
20,080,910
The anterior cingulate cortex receives thalamic afferents mainly from the midline and intralaminar nuclei rather than the anterior thalamic nuclei. In contrast, the posterior cingulate cortex receives afferents primarily from the anterior thalamic nuclei and from extensive cortical areas in the frontal, parietal, and t...
10.1038/nrn1704
The first demonstration of MITN projections to the cingulate cortex. These nuclei were later shown to project to many limbic areas in the primate cerebral cortex, including the anterior insula and orbitofrontal cortex, as well as the amygdala, and this projection system might be a network integrator for the limbic/medi...
10.1152/jn.1990.63.5.1118
50,895,633
1. Recordings were made in anesthetized monkeys from neurons in the medullary reticular formation (MRF) caudal to the obex. Responses of 19 MRF neurons to mechanical, thermal, and/or electrical stimulation were examined. MRF neurons exhibited convergence of nociceptive cutaneous inputs from widespread areas of the body...
10.1038/nrn1704
The first demonstration of the functional properties of neurons in the pronociceptive SRD nucleus in the monkey. As this nucleus projects to the parafascicular nucleus in the thalamus, it is a pivotal source of nociceptive input to the cingulate gyrus and partially explains the large receptive fields of nociceptive neu...
10.1126/science.1067176
20,666,574
It has been suggested that placebo analgesia involves both higher order cognitive networks and endogenous opioid systems. The rostral anterior cingulate cortex (rACC) and the brainstem are implicated in opioid analgesia, suggesting a similar role for these structures in placebo analgesia. Using positron emission tomogr...
10.1038/nrn1704
The first study to show colocalization of opioid binding and the opioid placebo in the cingulate cortex.
10.1523/jneurosci.2449-04.2004
123,585,307
We examined the neural encoding of synthetic and natural sounds by single neurons in the auditory system of male zebra finches by estimating the mutual information in the time-varying mean firing rate of the neuronal response. Using a novel parametric method for estimating mutual information with limited data, we teste...
10.1038/nrn3731
Using estimations of mutual information, this study shows that sounds that are otherwise identical in intensity and frequency but have a modulation power spectrum with natural distributions are more efficiently encoded in the avian auditory cortex.
10.1121/1.1624067
122,995,523
The modulation statistics of natural sound ensembles were analyzed by calculating the probability distributions of the amplitude envelope of the sounds and their time-frequency correlations given by the modulation spectra. These modulation spectra were obtained by calculating the two-dimensional Fourier transform of th...
10.1038/nrn3731
This paper introduces the joint temporal and spectral modulation power spectrum of sounds and shows that natural sounds have a characteristic signature in this representation.
10.1523/jneurosci.0966-10.2010
123,258,786
The efficient-coding hypothesis asserts that neural and perceptual sensitivity evolved to faithfully represent biologically relevant sensory signals. Here we characterized the spectrotemporal modulation statistics of several natural sound ensembles and examined how neurons encode these statistics in the central nucleus...
10.1038/nrn3731
In this study, Rodriguez et al . show that the modulation tuning of neurons in the inferior colliculus balances out the 1/ f relationship found in the modulation power spectrum of natural sounds to transmit modulation information efficiently, with reduced redundancy.
10.1152/jn.01025.2011
61,389,848
In the primary auditory cortex, spectrotemporal receptive fields (STRFs) are composed of multiple independent components that capture the processing of disparate stimulus aspects by any given neuron. The origin of these multidimensional stimulus filters in the central auditory system is unknown. To determine whether mu...
10.1038/nrn3731
In this study, Atencio et al . use the maximally informative dimension algorithm to extract multicomponent STRFs and show that the number of components needed to characterize auditory neurons is greater in the cortex than in the thalamus.
10.1523/jneurosci.2042-08.2009
81,795,200
Auditory perception depends on the coding and organization of the information-bearing acoustic features of sounds by auditory neurons. We report here that auditory neurons can be classified into functional groups, each of which plays a specific role in extracting distinct complex sound features. We recorded the electro...
10.1038/nrn3731
This study describes the STRFs found in the avian inferior colliculus and avian auditory cortex and shows how they form unique functional groups that extract distinct features of natural sounds that are in turn important for distinct percepts.
10.1126/science.1203980
104,421,539
A common plant pathogen induces the growth of disease-suppressive microbes in local soil communities.
10.1038/nrmicro3109
This paper describes a metataxonomic analysis of naturally disease-suppressive soil to identify consortia of rhizosphere bacteria that protect plants from fungal infections.
10.1098/rspb.2012.0285
17,590,770
Plant–soil feedbacks (PSFs) have gained attention for their role in plant community dynamics, but their role in productivity has been overlooked. We developed and tested a biomass-specific, multi-species model to examine the role of PSFs in diversity–productivity relationships. The model predicts a negative relationshi...
10.1038/nrmicro3109
A model (based on empirical data) that explains how overyielding in mixed plant communities can be explained by a net reduction of negative interactions between plants and (rhizosphere) soil biota.
10.1073/pnas.92.10.4197
107,110,164
Genetic resistance in plants to root diseases is rare, and agriculture depends instead on practices such as crop rotation and soil fumigation to control these diseases. "Induced suppression" is a natural phenomenon whereby a soil due to microbiological changes converts from conducive to suppressive to a soilborne patho...
10.1038/nrmicro3109
A founding paper on strategies for the genetic analysis of mechanisms of soil-borne-disease suppression by rhizobacteria.
10.1111/j.1526-100x.2008.00497.x
60,744,762
Understanding priority effects, in which one species in a habitat decreases the success of later species, may be essential for restoring native communities. Priority effects can operate in two ways: size‐asymmetric competition and creation of “soil legacies,” effects on soil that may last long after the competitive eff...
10.1038/nrmicro3109
A keystone paper showing that the effects of plant growth can be 'memorized' by soils because the plants can change biotic and abiotic soil properties such that the performance of subsequent plant species can be promoted or reduced. These specific effects on subsequent plant species might change the priorities of one p...
10.1126/science.289.5477.307
124,120,531
Since its classification nearly 80 years ago, the human pathogen Candida albicans has been designated as an asexual yeast. In this report, we describe the construction of C. albicans strains that were subtly altered at the mating-type–like ( MTL ) locus, a cluster of genes that resembles the mating-type loci of other f...
10.1038/nrmicro3236
This study provides the first demonstration that C. albicans can undergo sexual mating, in this case using strains that were inoculated into a mouse model of systemic infection.
10.1126/science.289.5477.310
40,699,515
Although the diploid fungus Candida albicans , a human pathogen, has been thought to have no sexual cycle, it normally possesses mating-type–like orthologs ( MTL ) of both of the Saccharomyces cerevisiae mating-type genes ( MAT ) a and α. When strains containing only MTL a or MTL α were constructed by the loss of one h...
10.1038/nrmicro3236
This study shows that C. albicans strains can mate, in this case using strains that were co-incubated on laboratory agar.
10.1126/science.285.5431.1271
18,509,256
Candida albicans , the most prevalent fungal pathogen in humans, is thought to lack a sexual cycle. A set of C. albicans genes has been identified that corresponds to the master sexual cycle regulators a1, α1, and α2 of the Saccharomyces cerevisiae mating-type ( MAT ) locus. The C. albicans genes are arranged in a way ...
10.1038/nrmicro3236
This study provides the first clue towards the discovery of a C. albicans sexual cycle by identifying a mating type-like locus.
10.1126/science.1128242
103,714,865
Resistance to the limited number of available antifungal drugs is a serious problem in the treatment of Candida albicans . We found that aneuploidy in general and a specific segmental aneuploidy, consisting of an isochromosome composed of the two left arms of chromosome 5, were associated with azole resistance. The iso...
10.1038/nrmicro3236
This paper reveals that chromosome aneuploidy drives increased drug resistance in clinical isolates of C. albicans
10.1126/science.175.4019.326
102,697,544
Twelve primary subcultures of Histoplasma capsulatum , paired in all possible combinations on agar containing yeast extract and Alphacel, produced fertile cleistothecia, resembling those of Ajellomyces dermatitidis ( Blastomyces dermatitidis ).
10.1038/nrmicro3236
This paper describes the existence of a sexual cycle in H. capsulatum
10.1126/science.156.3774.528
61,225,350
Growth of five combinations of strains of Blastomyces dermatitidis in paired cultures on yeast-extract agar, plus bone meal, yielded the perfect stage for the first time. These cleistothecia, apparently of a new genus, produced eight spored asci. Monoascospore cultures developed hyphae and conidia typical of B. dermati...
10.1038/nrmicro3236
This study is the first to identify a sexual cycle in B. dermatitidis
10.1128/jb.169.1.189-197.1987
18,921,688
A second high-frequency switching system was identified in selected pathogenic strains in the dimorphic yeast Candida albicans. In the characterized strain WO-1, cells switched heritably, reversibly, and at a high frequency (approximately 10(-2] between two phenotypes readily distinguishable by the size, shape, and col...
10.1038/nrmicro3236
This paper provides the first demonstration that C. albicans cells undergo the white–opaque switch.
10.1073/pnas.0605138103
17,609,699
White–opaque switching in the human fungal pathogen Candida albicans is an alternation between two distinct types of cells, white and opaque. White and opaque cells differ in their appearance under the microscope, the genes they express, their mating behaviors, and the host tissues for which they are best suited. Each ...
10.1038/nrmicro3236
References 168, 169 and 170 identify WOR1 TOS9 ) as the master transcription factor that regulates the opaque state in C. albicans
10.1073/pnas.1010485107
20,805,117
Coxiella burnetii is an obligate intracellular bacterial pathogen responsible for acute and chronic Q fever. This bacterium harbors a type IV secretion system (T4SS) highly similar to the Dot/Icm of Legionella pneumophila that is believed to be essential for its infectivity. Protein substrates of the Coxiella T4SS are ...
10.1038/nrmicro3049
Research establishing a shuttle vector and translocation assays for C. burnetii , leading to the identification of a large number of T4SS effectors and confirming the presence of a functional secretion system in C. burnetii during infection.
10.1126/science.1158160
107,308,490
Specialized secretion systems are used by many bacteria to deliver effector proteins into host cells that can either mimic or disrupt the function of eukaryotic factors. We found that the intracellular pathogens Legionella pneumophila and Coxiella burnetii use a type IV secretion system to deliver into eukaryotic cells...
10.1038/nrmicro3049
A paper that identifies ankyrin repeat proteins as T4SS effectors in C. burnetii and L. pneumophila , indicating that these proteins are conserved 4SS effectors.
10.1111/j.1365-2958.2007.05604.x
123,056,069
Summary Legionella pneumophila and Coxiella burnetii have been shown to utilize the icm/dot type IV secretion system for pathogenesis and recently a large number of icm / dot ‐translocated substrates were identified in L. pneumophila . Bioinformatic analysis has revealed that 13 of the genes encoding for L. pneumophila...
10.1038/nrmicro3049
A report showing that components of the T4SS and some putative T4SS effectors are co-regulated, implying that there is a link between, and temporal regulation of, the secretion apparatus and its effectors.
10.1073/pnas.1004380107
80,631,859
Coxiella burnetii and Legionella pneumophila are evolutionarily related pathogens with different intracellular infection strategies. C. burnetii persists within and is transmitted by mammalian hosts, whereas, L. pneumophila is found primarily in the environment associated with protozoan hosts. Although a type IV secret...
10.1038/nrmicro3049
An article which describes the only characterized C. burnetii T4SS effector that prevents host cell apoptosis by targeting pro-apoptotic protein p32.
10.1073/pnas.0501863102
109,118,337
Coxiella burnetii is an obligate intracellular bacterium and the etiological agent of the zoonotic disease Q fever. Acute human Q fever is characterized by flu-like symptoms that, in some cases, can result in a persistent infection that may reactivate months or years after initial exposure. Mechanisms by which this obl...
10.1038/nrmicro3049
A study showing that lipopolysaccharide is used by virulent C. burnetii to evade immune surveillance.
10.1128/iai.49.3.775-779.1985
122,895,304
The obligate intracellular bacterium Coxiella burnetii is the etiological agent of acute Q-fever and chronic endocarditis in humans and of several zoonotic infections. The DNA from a variety of these disease isolates was compared for homology to the plasmid QpH1, found in the Nine Mile strain. Three patterns of homolog...
10.1038/nrmicro3049
The proposal that pathotype-specific differences exist between clinical isolates of C. burnetii
10.1073/pnas.0812074106
29,175,794
The inability to propagate obligate intracellular pathogens under axenic (host cell-free) culture conditions imposes severe experimental constraints that have negatively impacted progress in understanding pathogen virulence and disease mechanisms. Coxiella burnetii , the causative agent of human Q (Query) fever, is an ...
10.1038/nrmicro3049
Work which characterizes the cell-free growth medium of C. burnetii and determines the anaerobic and acidophilic tropism of this bacterium.
10.1128/mmbr.61.2.136-169.1997
61,053,792
Bacterial pathogens employ a number of genetic strategies to cause infection and, occasionally, disease in their hosts. Many of these virulence factors and their regulatory elements can be divided into a smaller number of groups based on the conservation of similar mechanisms. These common themes are found throughout b...
10.1038/nrmicro732
Classic paper in the field that focuses on the contributions of microorganisms to the process of microbial pathogenesis.
10.1002/hipo.20320
124,513,933
Abstract The prevailing paradigm in cognitive neuroscience assumes that the brain can be best understood as consisting of modules specialised for different psychological functions. Within the field of memory, we assume modules for different kinds of memory. The most influential version of this view posits a module call...
10.1038/nrn2614
This paper provides a critical but stimulating perspective on the idea that the medial temporal lobe system is involved only in memory, with special emphasis on the functions of the perirhinal cortex.
10.1146/annurev.neuro.30.051606.094328
41,689,735
The ability to recognize a previously experienced stimulus is supported by two processes: recollection of the stimulus in the context of other information associated with the experience, and a sense of familiarity with the features of the stimulus. Although familiarity and recollection are functionally distinct, there ...
10.1038/nrn2614
This paper reviews current concepts of how familiarity and recollection memory are supported by regions in the medial temporal lobe and proposes that there is a distinction between recollection and familiarity in specific regions of the medial temporal lobe.
10.1126/science.1125572
103,833,149
Grid cells in the medial entorhinal cortex (MEC) are part of an environment-independent spatial coordinate system. To determine how information about location, direction, and distance is integrated in the grid-cell network, we recorded from each principal cell layer of MEC in rats that explored two-dimensional environm...
10.1038/nrn2614
This study provided evidence that information on location, direction and distance is integrated and updated in the grid cell network during navigation.
10.1002/hipo.20436
60,095,715
Abstract The rat limbic system contains a variety of location (place and grid) cells and directional (head direction; HD) cells, thought to be critical for navigation. The HD cells can be found throughout many portions of the hippocampal formation, as well as additional limbic cortical and subcortical regions. These HD...
10.1038/nrn2614
This study provides evidence that the mammillary bodies provide important information for the head-direction cells but not for the place cells in the hippocampus.
10.1126/science.8160015
103,468,285
The primate visual system is often divided into two channels, designated M and P, whose signals are relayed to the cerebral cortex by neurons in the magnocellular and parvicellular layers of the dorsal lateral geniculate nucleus. We have identified a third population of geniculocortical neurons in the dorsal lateral ge...
10.1038/nrn2619
This paper demonstrated that staining for calbindin or α-calcium/calmodulin-dependent protein kinase reveals a population of neurons in the primate LGN that are distinct from the magnocellular and parvocellular neurons. These are termed koniocellular neurons.
10.1073/pnas.89.8.3566
27,839,773
Visual information reaching striate cortex comes from parallel pathways, and the information is organized, or processed, by the layers and columns of striate cortex. To better understand how this is accomplished anatomically, we asked whether parallel pathways originating in the lateral geniculate nucleus (LGN), and te...
10.1038/nrn2619
This paper showed that neurons in the CO patches of V1 receive convergent input from the magnocellular and parvocellular recipient layers of V1.
10.1126/science.1057916
44,983,472
Relationships between the M and P retino-geniculo-cortical visual pathways and “dorsal” visual areas were investigated by measuring the sources of local excitatory input to individual neurons in layer 4B of primary visual cortex. We found that contributions of the M and P pathways to layer 4B neurons are dependent on c...
10.1038/nrn2619
This paper demonstrated that local inputs to layer 4B neurons in V1 depend on cell type. Spiny stellate neurons receive input only from the magnocellular-recipient layer 4Cα, whereas pyramidal neurons receive input from both layer 4Cα and the parvocellular-recipient layer 4Cβ.
10.1126/science.1067902
86,108,028
Current models partition the primate visual system into dorsal (magno) and ventral (parvo, konio) streams. Perhaps the strongest evidence for this idea has come from the pattern of projections between the primary visual area (V1) and the second visual area (V2). Prior studies describe three distinct pathways: magno to ...
10.1038/nrn2619
This paper demonstrated the connectivity between CO-defined modules in primate area V1 and those in area V2.
10.1126/science.271.5255.1582
83,073,615
A new mathematical model was used to analyze a detailed set of human immunodeficiency virus-type 1 (HIV-1) viral load data collected from five infected individuals after the administration of a potent inhibitor of HIV-1 protease. Productively infected cells were estimated to have, on average, a life-span of 2.2 days (h...
10.1038/nrmicro772
Refined estimates for the half-life of productively infected T lymphocytes and clearance rate of plasma virions.
10.1126/science.278.5341.1295
41,669,424
The hypothesis that quiescent CD4 + T lymphocytes carrying proviral DNA provide a reservoir for human immunodeficiency virus–type 1 (HIV-1) in patients on highly active antiretroviral therapy (HAART) was examined. In a study of 22 patients successfully treated with HAART for up to 30 months, replication-competent virus...
10.1038/nrmicro772
First report on the persistence of latently infected memory T lymphocytes despite suppressive HAART.
10.1111/j.1365-2796.2007.01890.x
4,896,425
Abstract. Introduction. Chronic kidney disease (CKD) predisposes to a 10‐ to 20‐fold increased cardiovascular risk. Patients undergo accelerated atherogenesis and vascular ageing. We investigated whether telomere attrition, a marker of cell senescence, contributes to this increased mortality risk. Methods. This is a cr...
10.1038/nrneph.2017.78
First-in-man description of accelerated ageing in renal disease associated with inflammation and telomere attrition.
10.1111/j.1365-2796.2007.01777.x
4,900,137
Abstract. Objective. The lifespan of dialysis patients is as short as in patients with metastatic cancer disease, mainly due to cardiovascular disease (CVD). DNA methylation is an important cellular mechanism modulating gene expression associated with ageing, inflammation and atherosclerotic processes. Design. DNA meth...
10.1038/nrneph.2017.78
Demonstration of the potential for epigenetic changes to affect renal disease.
10.1038/ncomms4746
20,717,167
Abstract In experimental animals, maternal diet during the periconceptional period influences the establishment of DNA methylation at metastable epialleles in the offspring, with permanent phenotypic consequences. Pronounced naturally occurring seasonal differences in the diet of rural Gambian women allowed us to test ...
10.1038/nrneph.2017.78
Seminal paper providing evidence that maternal nutrition impacts DNA methylation processes and health in offspring.
10.1002/hipo.10207
18,135,103
Abstract Animal studies on the effects of chronic variable stress during the peripubertal‐juvenile period on hippocampal structure and function are lacking. Twenty‐eight‐day‐old Sprague‐Dawley rats were subjected to random, variable physical or social stress regimens for 4 weeks. Hippocampal volume was found to continu...
10.1038/nrn2639
One of the first papers to show protracted effects of adolescent stress on adulthood stress reactivity in rodents.
10.1073/pnas.0705615105
103,981,426
Stress is known to induce dendritic hypertrophy in the basolateral amygdala (BLA) and to enhance anxiety. Stress also leads to secretion of glucocorticoids (GC), and the BLA has a high concentration of glucocorticoid receptors. This raises the possibility that stress-induced elevation in GC secretion might directly aff...
10.1038/nrn2639
This interesting study addressed endocrine effects on the brain, with a focus on the amygdala and anxiety (rather than on hippocampus and memory). Of note, a single dose of glucocorticoids was sufficient to induce changes in amygdala structure 10 days later, which might be useful to model in animals PTSD.
10.1192/bjp.bp.106.024877
19,193,183
Background Post-traumatic stress disorder (PTSD) has inconsistently been associated with lower levels of cortisol. Aims To compare basal cortisol levels in adults with current PTSD and in people without psychiatric disorder. Method Systematic review and meta-analysis. Standardised mean differences (SMD) in basal cortis...
10.1038/nrn2639
This paper presented the first meta-analysis of cortisol findings in PTSD, to elucidate the determinants of hypocortisolism and resolve the inconsistency in findings.
10.1126/science.6270791
107,984,884
Mid-aged rats were either adrenalectomized and chronically maintained, or left intact and treated daily for a 9- to 10-month period with a potent analog of the peptide adrenocorticotropin (residues 4 to 9), which has some stimulant properties, or with the neural stimulant pentylenetetrazole. All three treatments reduce...
10.1038/nrn2639
The first study to show that chronic exposure to high levels of glucocorticoids in rodents is associated with memory impairments and reduced hippocampal volume.
10.1002/imhj.10052
82,112,268
Abstract Animal studies have shown that mother–infant interactions can have long‐term impacts on areas of the brain that regulate fearful behavior and the physiology of stress. Here, the research on human infants and children is reviewed with an eye to whether early experiences have similar effects in our species. Rese...
10.1038/nrn2639
A superb paper that summarized the effects of stress during development and how this knowledge can be used to develop effective interventions.
10.1073/pnas.130110497
62,102,972
Increased accumulation of lipofuscin in cells of the retinal pigment epithelium (RPE) is seen in several forms of macular degeneration, a common cause of blindness in humans. A major fluorophore of lipofuscin is the toxic bis -retinoid, N -retinylidene- N -retinylethanolamine (A2E). Previously, we generated mice with a...
10.1038/nrn2007
Demonstrates the accumulation of A2E in both a human Stargardt disease patient's eyes and in a mouse model of Stargardt disease.
10.1073/pnas.222551899
41,702,800
Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch's membrane and are risk factors for developing age-related macular degeneration (AMD). The progression of AMD might be slowed or halted if the formation of drusen could be modulated. To work toward a molecular understanding ...
10.1038/nrn2007
Describes the use of mass spectrometry to define the composition of microdissected drusen, revealing a wide variety of components.
10.1126/science.1109557
125,249,620
Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene ( CFH ) is strong...
10.1038/nrn2007
References 73–76 are four initial reports of linkage between AMD susceptibility and sequence variation in the CFH gene.
10.4049/jimmunol.174.1.491
79,774,187
Abstract Choroidal neovascularization (CNV), or choroidal angiogenesis, is the hallmark of age-related macular degeneration and a leading cause of visual loss after age 55. The pathogenesis of new choroidal vessel formation is poorly understood. Although inflammation has been implicated in the development of CNV, the r...
10.1038/nrn2007
A convincing demonstration that there is an immunological component to experimental choroidal neovascularization, even if it is induced by a laser burn.
10.1073/pnas.0602131103
79,442,365
Oxidative stress has long been linked to the pathogenesis of neurodegenerative diseases; however, whether it is a cause or merely a consequence of the degenerative process is still unknown. We show that mice deficient in Cu, Zn-superoxide dismutase (SOD1) have features typical of age-related macular degeneration in hum...
10.1038/nrn2007
Describes genetic evidence that oxidative and photo-oxidative damage induce drusen formation in a mouse model of AMD.
10.1073/pnas.0737855100
102,716,983
Recessive Stargardt's macular degeneration is an inherited blinding disease of children caused by mutations in the ABCR gene. The primary pathologic defect in Stargardt's disease is accumulation of toxic lipofuscin pigments such as N -retinylidene- N -retinylethanolamine (A2E) in cells of the retinal pigment epithelium...
10.1038/nrn2007
Presents a mouse model of Stargardt disease in which pharmacological inhibition of RPE65 blocks A2E accumulation.
10.1073/pnas.0903438106
62,158,625
The ulcer-causing gastric pathogen Helicobacter pylori is the only bacterium known to colonize the harsh acidic environment of the human stomach. H. pylori survives in acidic conditions by producing urease, which catalyzes hydrolysis of urea to yield ammonia thus elevating the pH of its environment. However, the manner...
10.1038/nrmicro3016
Study showing that H. pylori is immobilized by gastric mucin gel at low pH but in the presence of urea induces a pH-dependent gel-to-solution transition that allows the bacterium to swim freely.
10.1073/pnas.1104598108
99,129,857
The host inflammatory response to chronic bacterial infections often dictates the disease outcome. In the case of the gastric pathogen Helicobacter pylori , host inflammatory responses result in outcomes that range from moderate and asymptomatic to more severe with concomitant ulcer or cancers. It was found recently th...
10.1038/nrmicro3016
Study demonstrating that chemotaxis promotes interactions between the bacteria and epithelium that drive pro-inflammatory T H 17 responses.
10.4049/jimmunol.0803293
26,970,502
Abstract Chronic infection with the bacterial pathogen Helicobacter pylori is a risk factor for the development of gastric cancer, yet remains asymptomatic in the majority of individuals. We report here that the C57BL/6 mouse model of experimental infection with the closely related Helicobacter felis recapitulates this...
10.1038/nrmicro3016
This paper revealed that T cell responses to H. pylori promote clearance on the one hand and immunopathology on the other hand, which complicates vaccine development.
10.1073/pnas.0308573100
38,195,583
Clinical isolates of Helicobacter pylori show marked diversity, which may derive from genomic changes that occur during the often lifelong association of the bacterium with its human host. We used the rhesus macaque model, together with DNA microarrays, to examine genomic changes in H. pylori that occur early during ex...
10.1038/nrmicro3016
This was the first demonstration of gene conversion as a mechanism for phase variation of adhesin expression during experimental infection.
10.1073/pnas.0711183105
38,415,965
Infection with cagA -positive Helicobacter pylori is associated with gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma of B cell origin. The cagA -encoded CagA protein is delivered into gastric epithelial cells via the bacterial type IV secretion system and, upon tyrosine phosphorylat...
10.1038/nrmicro3016
A study using transgenic expression to show that CagA can behave as an oncogene.
10.1126/science.1078599
16,762,676
Transit peptides mediate protein targeting into plastids and are only poorly understood. We extracted amino acid features from transit peptides that target proteins to the relict plastid (apicoplast) of malaria parasites. Based on these amino acid characteristics, we identified 466 putative apicoplast proteins in the P...
10.1038/nrmicro843
Shows, through mutational analysis, that charge is the main physiochemical property relevant to apicoplast transit peptide function, and describes a prediction algorithm based on these findings.
10.1126/science.285.5433.1573
125,260,666
A mevalonate-independent pathway of isoprenoid biosynthesis present in Plasmodium falciparum was shown to represent an effective target for chemotherapy of malaria. This pathway includes 1-deoxy- d -xylulose 5-phosphate (DOXP) as a key metabolite. The presence of two genes encoding the enzymes DOXP synthase and DOXP re...
10.1038/nrmicro843
First report of enzmyes from the DOXP isopentenyl diphosphate pathway in Plasmodium . It advances the DOXP pathway as a therapeutic target.
10.1046/j.1432-1327.2000.01707.x
100,747,472
We have analyzed the interaction of DnaK and plant Hsp70 proteins with the wild‐type ferredoxin‐NADP + reductase precursor (preFNR) and mutants containing amino‐acid replacements in the targeting sequence. Using an algorithm already developed [Rüdiger, S., Germeroth, L., Schneider‐Mergener, J. & Bukau, B. (1997) EM...
10.1038/nrmicro843
In vitro demonstration that Hsp70 chaperones bind to plant plastid transit peptides. An in silico analysis of 727 transit peptides binding sites indicates that they are enriched in Hsp70 binding sites.
10.1073/pnas.1011953108
20,754,493
We investigate swimming and chemotactic behaviors of the polarly flagellated marine bacteria Vibrio alginolyticus in an aqueous medium. Our observations show that V. alginolyticus execute a cyclic, three-step (forward, reverse, and flick) swimming pattern that is distinctively different from the run–tumble pattern adop...
10.1038/nrmicro3567
This study reported the discovery of the 'flick', a new reorientation mechanism found among marine bacteria, which makes their motility drastically different from the run-and-tumble motility observed in E. coli
10.1073/pnas.1105073108
60,525,286
Bacteria optimize the use of their motility appendages to move efficiently on a wide range of surfaces prior to forming multicellular bacterial biofilms. The “twitching” motility mode employed by many bacterial species for surface exploration uses type-IV pili (TFP) as linear actuators to enable directional crawling. I...
10.1038/nrmicro3567
This study revealed that P. aeruginosa twitching on surfaces are capable of a rapid slingshot motion that can efficiently reorient cells.
10.1073/pnas.1019079108
62,667,943
Bacterial processes ranging from gene expression to motility and biofilm formation are constantly challenged by internal and external noise. While the importance of stochastic fluctuations has been appreciated for chemotaxis, it is currently believed that deterministic long-range fluid dynamical effects govern cell–cel...
10.1038/nrmicro3567
This study reported the first experimental quantification of the flow field around a single swimming E. coli bacterium.
10.1073/pnas.1108608108
41,711,343
Sensory systems rescale their response sensitivity upon adaptation according to simple strategies that recur in processes as diverse as single-cell signaling, neural network responses, and whole-organism perception. Here, we study response rescaling in Escherichia coli chemotaxis, where adaptation dynamically tunes the...
10.1038/nrmicro3567
This study revealed experimentally that E. coli is capable of rescaling its chemotactic response, a process termed fold-change detection, which ensures high chemotactic sensitivity across a broad range of environmental conditions.
10.1073/pnas.1318943111
59,136,340
Significance The resource landscape for marine microbes is composed of microscale resource patches, but whether this microheterogeneity can drive the ecological differentiation of natural microbial populations remains unclear. The tradeoff between two nascent populations of marine bacteria demonstrated here is signific...
10.1038/nrmicro3567
This study revealed a competition–dispersal tradeoff among recently speciated sympatric marine bacteria, based on distinct behavioural interactions with particulate organic matter.
10.1126/science.284.5423.2168
61,017,492
Segmentation of the hindbrain and branchial region is a conserved feature of head development, involving the nested expression of Hox genes. Although it is presumed that vertebrate Hox genes function as segment identifiers, responsible for mediating registration between elements of diverse embryonic origin, this assump...
10.1038/nrn2254
This paper elegantly demonstrates that misexpression of Hoxb1 in presumptive trigeminal motor neurons converts them to an FBM fate.
10.1101/gad.1207204
102,248,100
Formation of neuronal circuits in the head requires the coordinated development of neurons within the central nervous system (CNS) and neural crest-derived peripheral target tissues. Hoxb1 , which is expressed throughout rhombomere 4 (r4), has been shown to be required for the specification of facial branchiomotor neur...
10.1038/nrn2254
This intriguing paper uses conditional deletion of Hoxb1 in the neural crest to show that r4 neural-crest-derived Schwann cells have a role in the maintenance and branching of FBM neurons.
10.1242/dev.127.7.1349
104,433,296
Motor neurons are a widely studied model of vertebrate neurogenesis. They can be subdivided in somatic, branchial and visceral motor neurons. Recent studies on the dorsoventral patterning of the rhombencephalon have implicated the homeobox genes Pax6 and Nkx2.2 in the early divergence of the transcriptional programme o...
10.1038/nrn2254
This paper uses knockout mice to show that PHOX2B has an important role in controlling the differentiation of BM and VM neuronal types in the hindbrain. In these mice, the neurons fail to differentiate and subsequently die.
10.1101/gad.255803
107,324,447
Neural progenitor cells often produce distinct types of neurons in a specific order, but the determinants that control the sequential generation of distinct neuronal subclasses in the vertebrate CNS remain poorly defined. We examined the sequential generation of visceral motor neurons and serotonergic neurons from a co...
10.1038/nrn2254
This important paper shows the sequential generation of BM, VM and serotonergic neurons from the V3 domain in the hindbrain, and the genetic control mechanisms that control this process at different axial levels.
10.1242/dev.01282
38,533,062
Little is known about the molecular mechanisms that integrate anteroposterior (AP) and dorsoventral (DV) positional information in neural progenitors that specify distinct neuronal types within the vertebrate neural tube. We have previously shown that in ventral rhombomere (r)4 of Hoxb1 and Hoxb2 mutant mouse embryos, ...
10.1038/nrn2254
This is an important paper in which the genes that regulate the patterning of the dorsoventral and rostrocaudal axes are found to converge in regulating PHOX2B expression and BM and VM neuron differentiation in r4.
10.1242/dev.02038
79,472,916
The floor plate is known to be a source of repellent signals for cranial motor axons, preventing them from crossing the midline of the hindbrain. However, it is unknown which molecules mediate this effect in vivo. We show that Slit and Robo proteins are candidate motor axon guidance molecules, as Robo proteins are expr...
10.1038/nrn2254
This study uses a combination of electroporation in chicks, in vitro assays and, importantly, in vivo evidence, to demonstrate a role for Slit–ROBO signalling in the repulsion of BM and VM axons away from the midline and towards their exit points.
10.1101/gr.122705.111
20,637,714
Immense populations of viruses are present in the human gut and other body sites. Understanding the role of these populations (the human “virome”) in health and disease requires a much deeper understanding of their composition and dynamics in the face of environmental perturbation. Here, we investigate viromes from hum...
10.1038/nrmicro2853
A longitudinal study of the impact of controlled diet changes on the human gut virome.
10.1073/pnas.1119061109
18,921,597
Genetic variation is critical in microbial immune evasion and drug resistance, but variation has rarely been studied in complex heterogeneous communities such as the human microbiome. To begin to study natural variation, we analyzed DNA viruses present in the lower gastrointestinal tract of 12 human volunteers by deter...
10.1038/nrmicro2853
The finding that hypervariable loci in the virome are predicted to encode Ig superfamily and C-type lectin folds.
10.1073/pnas.93.18.9926
40,647,639
Hippocampal neuron loss is widely viewed as a hallmark of normal aging. Moreover, neuronal degeneration is thought to contribute directly to age-related deficits in learning and memory supported by the hippocampus. By taking advantage of improved methods for quantifying neuron number, the present study reports evidence...
10.1038/nrn3200
This paper reports rigorous, quantitative evidence that neuron loss does not accompany age-related cognitive decline, reinforcing the search for structural and functional alterations short of neuron death that lead to cognitive decline.
10.1073/pnas.97.20.10954
61,144,297
Sandhoff disease is a lysosomal storage disorder characterized by the absence of β-hexosaminidase and storage of G M2 ganglioside and related glycolipids in the central nervous system. The glycolipid storage causes severe neurodegeneration through a poorly understood pathogenic mechanism. In symptomatic Sandhoff diseas...
10.1038/nrn1725
The first demonstration of a potentially causative role of microglia in the disease pathogenesis of a ganglioside storage disorder.
10.1098/rstb.2003.1269
66,905,615
Soon after the enzymatic defects in Gaucher disease and in Niemann–Pick disease were discovered, enzyme replacement or enzyme supplementation was proposed as specific treatment for patients with these and related metabolic storage disorders. While relatively straightforward in concept, successful implementation of this...
10.1038/nrn1725
A review of the history of the challenges involved in and the ultimate success of developing effective ERT for type 1 Gaucher disease.
10.1128/jb.172.8.4197-4205.1990
122,405,542
The nfo (endonuclease IV) gene of Escherichia coli is induced by superoxide generators such as paraquat (methyl viologen). An nfo'-lacZ operon fusion was used to isolate extragenic mutations affecting its expression. The mutations also affected the expression of glucose 6-phosphate dehydrogenase, Mn2(+)-superoxide dism...
10.1038/nrmicro3032
Along with reference 29, the two independent studies that discovered SoxRS.
10.1073/pnas.86.10.3484
101,171,579
The oxyR gene is required for the induction of a regulon of hydrogen peroxide-inducible genes in Escherichia coli and Salmonella typhimurium. The E. coli oxyR gene has been cloned and sequenced, revealing an open reading frame (305 amino acids) that encodes a 34.4-kDa protein, which is produced in maxicells carrying th...
10.1038/nrmicro3032
The discovery of OxyR, the transcription factor that responds to H 2 O 2
10.1073/pnas.96.11.6161
41,135,455
The Escherichia coli transcription factor OxyR is activated by the formation of an intramolecular disulfide bond and subsequently is deactivated by enzymatic reduction of the disulfide bond. Here we show that OxyR can be activated by two possible pathways. In mutants defective in the cellular disulfide-reducing systems...
10.1038/nrmicro3032
A quantification of the extreme reactivity of OxyR with H 2 O 2
10.1046/j.1365-2958.2003.03952.x
124,373,713
Summary In Escherichia coli , the SoxRS regulon confers resistance to redox‐cycling compounds, and the Mar regulon provides a defence against multiple antibiotics. The response regulators, SoxS and MarA, are synthesized de novo in response to their inducing signals and directly activate transcription of a common set of...
10.1038/nrmicro3032
A satisfying explanation for how SoxS is deactivated when stress subsides.
10.1126/science.1160619
82,899,512
It is thought that bacteria excrete redox-active pigments as antibiotics to inhibit competitors. In Pseudomonas aeruginosa , the endogenous antibiotic pyocyanin activates SoxR, a transcription factor conserved in Proteo- and Actinobacteria. In Escherichia coli , SoxR regulates the superoxide stress response. Bioinforma...
10.1038/nrmicro3032
A paper which articulates the idea that SoxR has a variety of roles in different bacteria.
10.1073/pnas.83.20.7731
122,702,778
Escherichia coli deficient in exonuclease III (xth gene mutants) are known to be hypersensitive to hydrogen peroxide. We now show that such mutants accumulate many more DNA single-strand breaks than do wild-type bacteria upon exposure to H2O2. DNA isolated from H2O2-treated xth- cells contains strand breaks that do not...
10.1038/nrmicro3032
A report establishing that certain DNA repair enzymes are dedicated to the repair of oxidative lesions.
10.1126/science.279.5357.1718
81,928,526
The OxyR transcription factor is sensitive to oxidation and activates the expression of antioxidant genes in response to hydrogen peroxide in Escherichia coli . Genetic and biochemical studies revealed that OxyR is activated through the formation of a disulfide bond and is deactivated by enzymatic reduction with glutar...
10.1038/nrmicro3032
The resolution of the mechanism by which OxyR senses H 2 O 2
10.1128/jb.179.18.5684-5692.1997
19,477,967
Previous studies have shown that the pyruvate-ferredoxin oxidoreductase (POR) of the sulfate-reducing bacterium Desulfovibrio africanus is a homodimer that contains one thiamine pyrophosphate and three [4Fe-4S]2+/1+ centers/subunit. Interestingly, the enzyme isolated from a strictly anaerobic bacterium is highly stable...
10.1038/nrmicro3032
Evidence that proteins might evolve to shield their oxidant-sensitive moieties from oxidants.
10.1042/bj3620001
123,271,375
The proteins of the MARCKS (myristoylated alanine-rich C kinase substrate) family were first identified as prominent substrates of protein kinase C (PKC). Since then, these proteins have been implicated in the regulation of brain development and postnatal survival, cellular migration and adhesion, as well as endo-, exo...
10.1038/nrn1324
A review focusing on recent studies of the MARCKS family of proteins.
10.1098/rstb.2002.1251
66,164,273
We have used a glutamate-specific dialysis electrode to obtain real-time measurements of changes in the concentration of glutamate in the extracellular space of the hippocampus during low-frequency stimulation and following the induction of long-term potentiation (LTP). In the dentate gyrus, stimulation of the perforan...
10.1038/nrn1324
One of many excellent reviews of LTP that were published in issue 1432 of Philosophical Transactions
10.1126/science.287.5451.248
38,447,845
The memory consolidation hypothesis proposed 100 years ago by Müller and Pilzecker continues to guide memory research. The hypothesis that new memories consolidate slowly over time has stimulated studies revealing the hormonal and neural influences regulating memory consolidation, as well as molecular and cellular mec...
10.1038/nrn1324
An invaluable review of neural and hormonal systems in memory consolidation.
10.1101/gad.205501
65,382,552
Conformational changes in sigma 54 (ς 54 ) and ς 54 -holoenzyme depend on nucleotide hydrolysis by an activator. We now show that ς 54 and its holoenzyme bind to the central ATP-hydrolyzing domains of the transcriptional activators PspF and NifA in the presence of ADP–aluminum fluoride, an analog of ATP in the transiti...
10.1038/nrmicro954
Describes a stable interaction between σ 54 and the transcriptional activator protein in the presence of a transition state analogue for ATP hydrolysis.
10.1073/pnas.1300886110
62,493,114
Stress and glucocorticoid hormones regulate hippocampal neurogenesis, but the molecular mechanisms mediating these effects are poorly understood. Here we identify the glucocorticoid receptor (GR) target gene, serum- and glucocorticoid-inducible kinase 1 (SGK1), as one such mechanism. Using a human hippocampal progenito...
10.1038/nrn3855
This paper (by our group) describes a series of cellular, animal and clinical studies showing that SGK1 is one of the mechanisms by which glucocorticoids affect neurogenesis, with actions both upstream and downstream of the glucocorticoid receptor.
10.1073/pnas.0708092105
104,097,827
Stress decreases neurogenesis in the adult hippocampus, and blockade of this effect is required for the actions of antidepressants in behavioral models of depression. However, the mechanisms underlying these effects of stress have not been identified. Here, we demonstrate an essential role for the proinflammatory cytok...
10.1038/nrn3855
The first paper to examine the role of inflammation in stress-induced inhibition of neurogenesis.
10.1073/pnas.0709102105
123,162,334
Glucocorticoids (GCs) display both protective and destructive effects in the nervous system. In excess, GCs produce neuronal damage after stress or brain injury; however, the neuroprotective effects of adrenal steroids also have been reported. The mechanisms that account for the positive actions are not well understood...
10.1038/nrn3855
This paper examines the potential crosstalk between neurotrophin signalling pathways and the glucocorticoid receptor, with potential implications for adult neurogenesis.
10.1210/mend.15.10.0706
45,348,453
Abstract Brain-derived neurotrophic factor has been associated previously with the regulation of food intake. To help elucidate the role of this neurotrophin in weight regulation, we have generated conditional mutants in which brain-derived neurotrophic factor has been eliminated from the brain after birth through the ...
10.1038/nrn.2016.24
This study demonstrated that BDNF expressed in the brain is essential for the control of energy balance.
10.1073/pnas.94.12.6456
16,741,938
Receptor subunits for the neurocytokine ciliary neurotrophic factor (CNTF) share sequence similarity with the receptor for leptin, an adipocyte-derived cytokine involved in body weight homeostasis. We report here that CNTF and leptin activate a similar pattern of STAT factors in neuronal cells, and that mRNAs for CNTF ...
10.1038/nrn.2016.24
This study showed that CNTF could overcome leptin resistance to reduce obesity-related phenotypes in mice.
10.1210/en.2012-1024
22,956,145
Leptin resistance is a feature of obesity that poses a significant therapeutic challenge. Any treatment that is effective to reduce body weight in obese patients must overcome or circumvent leptin resistance, which promotes the maintenance of excess body fat in obese individuals. Ciliary neurotrophic factor (CNTF) is u...
10.1038/nrn.2016.24
This study, using a genetic approach, showed that CNTF and leptin acted on distinct neuronal populations to suppress food intake.
10.1126/science.1115360
124,023,113
Ciliary neurotrophic factor (CNTF) induces weight loss in obese rodents and humans, and for reasons that are not understood, its effects persist after the cessation of treatment. Here we demonstrate that centrally administered CNTF induces cell proliferation in feeding centers of the murine hypothalamus. Many of the ne...
10.1038/nrn.2016.24
This study shows that CNTF might induce long-term weight loss by stimulating adult neurogenesis in the hypothalamus.
10.1242/dev.125.3.507
62,659,707
We have investigated the role of Bone Morphogenetic Protein 4 (BMP-4) and a BMP antagonist, chordin, in primitive streak formation and neural induction in amniote embryos. We show that both BMP-4 and chordin are expressed before primitive streak formation, and that BMP-4 expression is downregulated as the streak starts...
10.1038/nrn786
Chordin-expressing grafted cells were shown to induce a secondary axis in chick embryos. This work challenged the idea that BMP inhibitors from the node impart neural fates to the ectoderm in chick embryos.