source_doi stringlengths 13 57 | source_mag_paper_id int64 490k 157M | source_abstract stringlengths 8 10.7k | target_doi stringlengths 14 27 | target_summary stringlengths 42 889 |
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10.1083/jcb.119.4.893 | 107,279,919 | Cells in culture reveal high levels of protein tyrosine phosphorylation in their focal adhesions, the regions where cells adhere to the underlying substratum. We have examined the tyrosine phosphorylation of proteins in response to plating cells on extracellular matrix substrata. Rat embryo fibroblasts, mouse Balb/c 3T... | 10.1038/35099066 | This and the previous study initiated a cascade of publications showing that the formation of focal adhesions is accompanied by tyrosine phosphorylation of their main components. |
10.1101/gad.9.12.1505 | 83,284,329 | We have explored the role of the tyrosine kinase c-Src in cellular adhesion. Fibroblasts derived from src-/- mice (src-/- fibroblasts) exhibit a reduced rate of spreading on fibronectin. These defect is rescued by expression of wild-type chicken c-Src. Analyses of mutants suggest that c-Src increases the rate of cell s... | 10.1038/35099066 | This study first showed the involvment of pp60 c-src in the regulation of cell–matrix adhesion. |
10.1083/jcb.148.5.1075 | 41,676,499 | Fibronectin matrix assembly is a multistep, integrin-dependent process. To investigate the role of integrin dynamics in fibronectin fibrillogenesis, we developed an antibody-chasing technique for simultaneous tracking of two integrin populations by different antibodies. We established that whereas the vitronectin recep... | 10.1038/35099066 | Direct demonstration of the specific translocation of α 5 β 1 integrin from focal adhesions to, and along, fibrillar adhesions that drive the formation of fibronectin matrix. |
10.1083/jcb.141.2.539 | 41,632,587 | Many factors influence the assembly of fibronectin into an insoluble fibrillar extracellular matrix. Previous work demonstrated that one component in serum that promotes the assembly of fibronectin is lysophosphatidic acid (Zhang, Q., W.J. Checovich, D.M. Peters, R.M. Albrecht, and D.F. Mosher. 1994. J. Cell Biol. 127:... | 10.1038/35099066 | This paper links cell contractility regulated by Rho and stretch-induced exposure of cryptic assembly sites in fibronectin to provide mechanistic insight into matrix assembly. |
10.1083/jcb.200102034 | 20,783,883 | Fibronectin (FN) assembly into a fibrillar extracellular matrix is a stepwise process requiring participation from multiple FN domains. Fibril formation is regulated in part by segments within the first seven type III repeats (III1–7). To define the specific function(s) of this region, recombinant FNs (recFNs) containi... | 10.1038/35099066 | The latest publication in ongoing studies to identify the key binding sites in fibronectin, which points to repeating unit III 2 as particularly important for matrix assembly. |
10.1073/pnas.96.5.2153 | 125,149,572 | Fibronectin (FN) forms the primitive fibrillar matrix in both embryos and healing wounds. To study the matrix in living cell cultures, we have constructed a cell line that secretes FN molecules chimeric with green fluorescent protein. These FN–green fluorescent protein molecules were assembled into a typical matrix tha... | 10.1038/35099066 | The first paper to document stretching of fibronectin in living cells using green fluorescent protein (GFP). |
10.1126/science.274.5286.373 | 17,701,723 | The human adenovirus E1B gene encodes a 55-kilodalton protein that inactivates the cellular tumor suppressor protein p53. Here it is shown that a mutant adenovirus that does not express this viral protein can replicate in and lyse p53-deficient human tumor cells but not cells with functional p53. Ectopic expression of ... | 10.1038/35101008 | First virus described for which replication depends on loss of p53. This adenovirus mutant grows selectively in tumour cells in which p53 is inactive, but also depends on other functions of tumour cells that are not fully understood for its efficient replication. In this paper, it was shown for the first time that a re... |
10.1126/science.220.4594.268 | 61,553,035 | Most of the morphological and functional differences between vertebrates and other chordates occur in the head and are derived embryologically from muscularized hypomere, neural crest, and epidermal (neurogenic) placodes. In the head, the neural crest functions as mesoderm and forms connective, skeletal, and muscular t... | 10.1038/35076601 | A classic paper that crystallizes thinking about the importance of the neural crest in vertebrate evolution. |
10.1242/dev.127.8.1671 | 104,424,466 | Neural crest cells are multipotential stem cells that contribute extensively to vertebrate development and give rise to various cell and tissue types. Determination of the fate of mammalian neural crest has been inhibited by the lack of appropriate markers. Here, we make use of a two-component genetic system for indeli... | 10.1038/35076601 | This paper describes an elegant use of Cre-loxP technology to mark the cranial neural crest, by causing LacZ to be expressed by neural-crest cells. |
10.1101/gad.9.21.2646 | 83,424,042 | The anterior part of the vertebrate head expresses a group of homeo box genes in segmentally restricted patterns during embryogenesis. Among these, Otx2 expression covers the entire fore- and midbrains and takes place earliest. To examine its role in development of the rostral head, a mutation was introduced into this ... | 10.1038/35076601 | Hox genes are not expressed anterior to the second branchial arch or rhombomere 3, so other transcription factors must be involved in patterning more rostral structures. This work identifies Otx2 as having this role in mammals — a role that might be extremely ancient (see references 10 – 12 |
10.1073/pnas.97.26.14536 | 79,690,039 | Craniosynostosis syndromes are autosomal dominant human skeletal diseases that result from various mutations in fibroblast growth factor receptor genes ( Fgfrs ). Apert syndrome (AS) is one of the most severe craniosynostosis syndromes and is associated with severe syndactyly of the hands and feet and with central nerv... | 10.1038/35076601 | This paper indicated that specific mutations in the extracellular region of FGFR2 confer a gain of function by increasing the repertoire of ligands that receptor isoforms can bind. |
10.1242/dev.108.1.19 | 62,606,469 | We have used the quail-chick chimera system to reveal the cell migrations and settling pattern involved in the construction of the cerebellum. Three types of orthotopic transplantations were carried out, between quail and chick embryos, at the 12-somite stage: exchanges of (i) the whole metencephalic vesicle, (ii) the ... | 10.1038/35081558 | Describes the lineage analysis experiments that revealed the dual origin of the cerebellum from the mesencephalon and metencephalon. |
10.1146/annurev.neuro.22.1.511 | 62,532,622 | ▪ Abstract Widespread cell migrations are the hallmark of vertebrate brain development. In the early embryo, morphogenetic movements of precursor cells establish the rhombomeres of the hindbrain, the external germinal layer of the cerebellum, and the regional boundaries of the forebrain. In midgestation, after primary ... | 10.1038/35081558 | This review synthesizes recent advances in our understanding of neuronal migration. |
10.1073/pnas.91.8.3228 | 82,981,606 | We have examined the role of cyclooxygenase 2 (COX-2) in a model of inflammation in vivo. Carrageenan administration to the subcutaneous rat air pouch induces a rapid inflammatory response characterized by high levels of prostaglandins (PGs) and leukotrienes in the fluid exudate. The time course of the induction of COX... | 10.1038/35094017 | This study established 'proof of principle' that selective inhibition of COX-2 offered the anti-inflammatory activity, but lacked the gastrointestinal side effects of non-selective NSAIDs. |
10.1002/jso.2930240119 | 101,810,448 | Abstract Four members of a Gardner's syndrome family had rectal and colon polyposis treated with nonsteroid anti‐inflammatory drugs. Three of these patients had had subtotal colectomy and ileoproctostomy and the residual polyps arose in the rectal mucosa. The polyps almost completely disappeared when sulindac was admin... | 10.1038/35094017 | The first clinical observation that NSAIDs could cause the regression of intestinal polyps. |
10.1084/jem.190.4.451 | 38,573,224 | In this study, we use primary embryonic fibroblasts derived from cyclooxygenase-deficient transgenic embryos to further investigate the role of the two cyclooxygenases, cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), in the process of neoplastic transformation. Cells with either, neither, or both of the cyclooxy... | 10.1038/35094017 | Describes the first genetic evidence that high doses of NSAIDs can induce apoptosis independently of COX-1 or COX-2. |
10.1242/jcs.106.4.1153 | 20,786,498 | To contribute to a deeper understanding of M-phase control in eukaryotic cells, we have constructed a model based on the biochemistry of M-phase promoting factor (MPF) in Xenopus oocyte extracts, where there is evidence for two positive feedback loops (MPF stimulates its own production by activating Cdc25 and inhibitin... | 10.1038/35103078 | The first comprehensive model of cell-cycle regulation, carefully compared with experiments on intact frog embryos and cell-free egg extracts. |
10.1091/mbc.4.5.469 | 61,182,092 | We have developed a computer program that simulates the intracellular reactions mediating the rapid (nonadaptive) chemotactic response of Escherichia coli bacteria to the attractant aspartate and the repellent Ni2+ ions. The model is built from modular units representing the molecular components involved, which are eac... | 10.1038/35103078 | A trend-setting analysis of the molecular machinery that controls bacterial locomotion. Computer simulations reproduce the behaviour of more than 30 mutants in which components of the network are deleted or overexpressed. |
10.1073/pnas.74.12.5647 | 60,446,359 | Regulation by a repressor protein is the mechanism selected when, in the organism's natural environment, there is low demand for expression of the regulated structural genes. Regulation by an activator protein is selected when there is high demand for expression of the regulated structural genes. These general conclusi... | 10.1038/35103078 | An early and excellent application of dynamical reasoning to bacterial cell physiology. |
10.1073/pnas.94.13.6664 | 60,513,051 | Mammalian nucleotide excision repair (NER) eliminates carcinogen–DNA adducts by double endonucleolytic cleavage and subsequent release of 24–32 nucleotide-long single-stranded fragments. Here we manipulated the deoxyribose–phosphate backbone of DNA to analyze the mechanism by which damaged strands are discriminated as ... | 10.1038/35094000 | An excellent contribution to recent models for the molecular basis of damage recognition during NER. |
10.1126/science.276.5321.2045 | 83,454,674 | Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromoso... | 10.1038/35081564 | A missense mutation in the α-synuclein gene (A53T) causes early-onset familial Parkinson's disease in the Contursi kindred. The first known genetic cause of Parkinson's disease. |
10.1002/ana.410270309 | 124,107,825 | Abstract We report two large kindreds with Parkinson's disease (PD) apparently inherited in autosomal dominant fashion. Forty‐one persons in four generations have been affected; we have examined 7 of them. The two kindreds originated in a single small town in southern Italy and therefore are probably related. The illne... | 10.1038/35081564 | Description of an early-onset familial form of Parkinson's disease with autopsy-confirmed Lewy body pathology in the Contursi kindred. |
10.1126/science.289.5477.304 | 83,479,831 | p53 plays an essential pro-apoptotic role, a function thought to be shared with its family members p73 and p63. Here, we show that p73 is primarily present in developing neurons as a truncated isoform whose levels are dramatically decreased when sympathetic neurons apoptose after nerve growth factor (NGF) withdrawal. I... | 10.1038/35043127 | Analysis of sympathetic ganglia of TP73 knockout mice reveals a 50% reduction of neurons, which die in the absence of nerve growth factor in a p53-dependent manner. ΔN-p73, the main p73 product in sympathetic neurons of wild-type animals, is shown to have the capacity to prevent cell death after nerve growth factor wit... |
10.1002/ijc.21209 | 108,554,754 | Abstract The original article to which this Erratum refers was published in International Journal of Cancer (2005) 115(1) 74–84 DOI: 10.1002/ijc.20856 | 10.1038/35043127 | An interesting paper showing that the high levels of ΔN-p63 in immature keratinocytes must be eradicated for p53 to function. |
10.1126/science.278.5345.1950 | 125,080,592 | It is now commonly accepted that planning and execution of movements are based on distributed processing by neuronal populations in motor cortical areas. It is less clear, though, how these populations organize dynamically to cope with the momentary computational demands. Simultaneously recorded activities of neurons i... | 10.1038/35094565 | A study describing synchrony among motor neurons during anticipation of a GO cue. Temporal correlation is enhanced at time points when the animal expects the cue to appear. |
10.1073/pnas.97.26.14748 | 124,116,898 | Perception and cortical responses are not only driven “bottom-up” by the external stimulus but are altered by internal constraints such as expectancy or the current behavioral goal. To investigate neurophysiological mechanisms of such top-down effects, we analyzed the temporal interactions of neurons on different level... | 10.1038/35094565 | The paper describes synchrony between visual areas in awake cats during a GO/NO-GO task. Depending on the behavioural significance of the stimulus, interareal interactions occur in different frequency bands. Phase relations are compatible with top–down processing. |
10.1162/jocn.1996.8.6.603 | 109,099,414 | Recent experimental results in the visual cortex of cats and monkeys have suggested an important role for synchronization of neuronal activity on a millisecond time scale. Synchronization has been found to occur selectively between neuronal responses to related image components. This suggests that not only the firing r... | 10.1038/35094565 | A model is presented of how synchrony could be relevant for dynamic response selection during sensorimotor processing. |
10.1126/science.1055465 | 123,192,102 | In crowded visual scenes, attention is needed to select relevant stimuli. To study the underlying mechanisms, we recorded neurons in cortical area V4 while macaque monkeys attended to behaviorally relevant stimuli and ignored distracters. Neurons activated by the attended stimulus showed increased gamma-frequency (35 t... | 10.1038/35094565 | This paper shows that in monkey V4, attention enhances the coupling between spikes and field potentials, reflecting a coherent local population, in a spatially selective manner. This effect occurs in ongoing activity during stimulus expectation. |
10.1126/science.286.5446.1943 | 123,109,775 | The relation between the activity of a single neocortical neuron and the dynamics of the network in which it is embedded was explored by single-unit recordings and real-time optical imaging. The firing rate of a spontaneously active single neuron strongly depends on the instantaneous spatial pattern of ongoing populati... | 10.1038/35094565 | A very important paper showing that patterning of ongoing activity is related to the functional architecture of the cortical network. |
10.1152/jn.1993.70.5.2181 | 20,525,660 | 1. Subthreshold membrane potential oscillations have been observed in different types of CNS neurons. In this in vitro study, we examined the possible role of these oscillations by analyzing the responses of neurons from the inferior olivary nucleus to a combined stimulation of sine wave and synaptic potentials. 2. A n... | 10.1038/35094565 | This and the subsequent paper are important in vitro studies showing that subthreshold oscillations of the membrane potential of a cell lead to latency shifts of inputs and, hence, provide precise temporal windows for creating synchronized patterns in neural activity. |
10.1126/science.281.5380.1185 | 81,393,732 | Experiences are remembered or forgotten, but the neural determinants for the mnemonic fate of experience are unknown. Event-related functional magnetic resonance imaging was used to identify specific brain activations that differentiated between visual experiences that were later remembered well, remembered less well, ... | 10.1038/35049064 | Event-related-MRI study showing how different patterns of brain activation at encoding predict retrieval success. |
10.1126/science.8171325 | 125,203,973 | In a search for genes that regulate circadian rhythms in mammals, the progeny of mice treated with N -ethyl- N -nitrosourea (ENU) were screened for circadian clock mutations. A semidominant mutation, Clock , that lengthens circadian period and abolishes persistence of rhythmicity was identified. Clock segregated as a s... | 10.1038/35038557 | This study was the first to successfully use random mutagenesis, phenotype-based screening and positional cloning (that is, a forward-genetic approach) in mice. |
10.1073/pnas.96.15.8567 | 122,097,704 | We selected peptide aptamers from combinatorial libraries that disrupted cell-cycle arrest caused by mating pheromone in yeast. We used these aptamers as baits in two-hybrid hunts to identify genes involved in cell-cycle arrest. These experiments identified genes known to function in the pathway, as well as a protein k... | 10.1038/35038557 | This is the first successful use of peptide aptamers in a forward chemical-genetic screen. |
10.1111/j.1399-3011.1991.tb00765.x | 62,228,052 | A method is suggested for the synthesis of multicomponent peptide mixtures. The method is a solid phase synthesis modified in order to give a closely equimolar mixture of peptides with predetermined sequences. The main point of modification is that before every coupling cycle the resin is divided into equal parts and e... | 10.1038/35038557 | References 29 and 30 describe split-pool synthesis, a revolutionary method for synthesizing very large chemical libraries. |
10.1126/science.282.5389.737 | 81,463,138 | Nonpeptide agonists of each of the five somatostatin receptors were identified in combinatorial libraries constructed on the basis of molecular modeling of known peptide agonists. In vitro experiments using these selective compounds demonstrated the role of the somatostatin subtype-2 receptor in inhibition of glucagon ... | 10.1038/35038557 | These authors were the first to apply reverse chemical-genetics to a protein family. They identify specific small molecule partners of each member of a family of somatostatin cell-surface receptors. |
10.1126/science.272.5260.408 | 125,150,432 | Trapoxin is a microbially derived cyclotetrapeptide that inhibits histone deacetylation in vivo and causes mammalian cells to arrest in the cell cycle. A trapoxin affinity matrix was used to isolate two nuclear proteins that copurified with histone deacetylase activity. Both proteins were identified by peptide microseq... | 10.1038/35038557 | The authors demonstrate the power of affinity chromatography and biochemical purification to identify the protein target of the natural product trapoxin. |
10.1073/pnas.90.17.8033 | 123,039,874 | The restricted host-cell range and low titer of retroviral vectors limit their use for stable gene transfer in eukaryotic cells. To overcome these limitations, we have produced murine leukemia virus-derived vectors in which the retroviral envelope glycoprotein has been completely replaced by the G glycoprotein of vesic... | 10.1038/35038533 | Use of vesicular stomatitis virus glycoprotein (VSVG) to replace the envelope protein in MLV vectors. The resulting chimeric virus, containing VSVG protein, is pantropic and can be concentrated by ultracentrifugation. |
10.1073/pnas.85.9.3150 | 58,474,137 | Mouse primary skin fibroblasts were infected with a recombinant retrovirus containing human factor IX cDNA. Bulk infected cells capable of synthesizing and secreting biologically active human factor IX protein were embedded in collagen, and the implant was grafted under the epidermis. Sera from the transplanted mice co... | 10.1038/35038533 | On transplantation of retrovirally-transduced mouse fibroblasts, producing and secreting human factor IX protein, the transcription of the transgene is `shut off'. |
10.1126/science.272.5259.263 | 82,900,657 | A retroviral vector system based on the human immunodeficiency virus (HIV) was developed that, in contrast to a murine leukemia virus-based counterpart, transduced heterologous sequences into HeLa cells and rat fibroblasts blocked in the cell cycle, as well as into human primary macrophages. Additionally, the HIV vecto... | 10.1038/35038533 | The first use of a lentiviral vector to transduce genes in vitro and in vivo in non-dividing cells. The lentiviral vector was packaged in VSVG envelope protein to expand the host range. |
10.1073/pnas.93.24.13565 | 20,821,134 | Adenoviruses are attractive vectors for the delivery of foreign genes into mammalian cells for gene therapy. However, current vectors retain many viral genes that, when expressed at low levels, contribute to the induction of a host immune response against transduced cells. We have developed a helper-dependent packaging... | 10.1038/35038533 | References 42 and 43 describe the generation of new adenoviral, `gutless', vectors in which all the viral genes required for viral propagation are provided in trans . The gutless vectors show long-term expression of the transgene. |
10.1073/pnas.95.19.11377 | 65,352,333 | Replication-defective adenoviral (RDAd) vectors can be generated at high titers and infect both dividing and nondividing cells. Long term expression in the transduced tissue, however, has been a problem because of the cellular immune responses against the infected cells. We demonstrate that mice injected with RDAd vect... | 10.1038/35038533 | Even physically inactivated adenoviral particles can generate a cytotoxic T-cell response, raising concerns about adenoviral vectors as suitable tools for long-term gene therapy. |
10.1126/science.288.5466.669 | 83,484,463 | Severe combined immunodeficiency–X1 (SCID-X1) is an X-linked inherited disorder characterized by an early block in T and natural killer (NK) lymphocyte differentiation. This block is caused by mutations of the gene encoding the γc cytokine receptor subunit of interleukin-2, -4, -7, -9, and -15 receptors, which particip... | 10.1038/35038533 | The first definitive example of successful gene therapy, in three children suffering from SCID-XI. The haematopoietic stem cells from the patients were transduced by recombinant retroviruses expressing the γc–subunit, which is common to many interleukin receptors. |
10.1073/pnas.89.12.5547 | 83,370,931 | Control elements of the tetracycline-resistance operon encoded in Tn10 of Escherichia coli have been utilized to establish a highly efficient regulatory system in mammalian cells. By fusing the tet repressor with the activating domain of virion protein 16 of herpes simplex virus, a tetracycline-controlled transactivato... | 10.1038/35038533 | First description of a regulable gene expression system that uses tetracycline. The transgene is `turned off' in the presence of tetracycline and `turned on' in its absence. |
10.1126/science.8346443 | 83,411,395 | The apolipoprotein E type 4 allele ( APOE -ε4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE -ε4 alleles in 42 families with late onset... | 10.1038/35036221 | References 5 and 6 describe how ApoE4 is found to predispose carriers to late-onset AD. |
10.1083/jcb.133.2.269 | 122,539,495 | No targeting sequence for peroxisomal integral membrane proteins has yet been identified. We have previously shown that a region of 67 amino acids is necessary to target Pmp47, a protein that spans the membrane six times, to peroxisomes. This region comprises two membrane spans and the intervening loop. We now demonstr... | 10.1038/35073063 | A detailed analysis of the first identified peroxisomal membrane targeting signal. |
10.1091/mbc.10.12.4005 | 78,193,848 | Pichia pastoris PEX17 was cloned by complementation of a peroxisome-deficient strain obtained from a novel screen for mutants disrupted in the localization of a peroxisomal membrane protein (PMP) reporter. PEX17 encodes a 267-amino-acid protein with low identity (18%) to the previously characterizedSaccharomyces cerevi... | 10.1038/35073063 | Evidence for the existence of multiple subcomplexes containing separable pools of peroxins. |
10.1091/mbc.6.6.675 | 102,165,257 | By virtue of their synthesis in the cytoplasm, proteins destined for import into peroxisomes are obliged to traverse the single membrane of this organelle. Because the targeting signal for most peroxisomal matrix proteins is a carboxy-terminal tripeptide sequence (SKL or its variants), these proteins must remain import... | 10.1038/35073063 | The largest nondeformable structure, a colloidal gold particle, able to traverse the peroxisomal membrane is at least 9 nm in diameter. |
10.1083/jcb.144.2.255 | 125,148,829 | Zellweger syndrome and related diseases are caused by defective import of peroxisomal matrix proteins. In all previously reported Zellweger syndrome cell lines the defect could be assigned to the matrix protein import pathway since peroxisome membranes were present, and import of integral peroxisomal membrane proteins ... | 10.1038/35073063 | A model for two overlapping, multistep pathways of peroxisome assembly in human fibroblasts. |
10.1083/jcb.148.1.29 | 122,545,307 | We have identified and purified six subforms of peroxisomes, designated P1 to P6, from the yeast, Yarrowia lipolytica. An analysis of trafficking of peroxisomal proteins in vivo suggests the existence of a multistep peroxisome assembly pathway in Y. lipolytica. This pathway operates by conversion of peroxisomal subform... | 10.1038/35073063 | Evidence for the existence of a multistep peroxisome assembly pathway that operates by the ordered conversion of structurally distinct peroxisomal subforms to mature peroxisomes. |
10.1083/jcb.135.1.123 | 122,845,847 | Pex11p (formerly Pmp27) has been implicated in peroxisomal proliferation (Erdmann, R., and G. Blobel. 1995. J. Cell Biol. 128; 509-523; Marshall, P.A., Y.I. Krimkevich, R.H. Lark, J.M. Dyer, M. Veenhuis, and J.M. Goodman, 1995. J. Cell Biol. 129; 345-355). In its absence, peroxisomes in Saccharomyces cerevisiae fail to... | 10.1038/35073063 | A detailed analysis of the mechanism of Pex11 action in regulating division of yeast peroxisomes from within the organelle. |
10.1083/jcb.141.2.373 | 18,541,492 | Peroxisomal membrane protein (Pmp)26p (RnPex11p), a major constituent of induced rat liver peroxisomal membrane, was found to contain a COOH-terminal, cytoplasmically exposed consensus dilysine motif with the potential to bind coatomer. Biochemical as well as immunocytochemical evidence is presented showing that peroxi... | 10.1038/35073063 | Evidence that the recruitment of ARF and coatomer by Pex11, which resides on the cytosolic face of mammalian peroxisomes, might initiate fission and/or budding of these organelles followed by their division. |
10.1084/jem.186.2.239 | 20,489,822 | In this report, we show that cross-presentation of self-antigens can lead to the peripheral deletion of autoreactive CD8+ T cells. We had previously shown that transfer of ovalbumin (OVA)-specific CD8+ T cells (OT-I cells) into rat insulin promoter–membrane-bound form of OVA transgenic mice, which express the model aut... | 10.1038/35100512 | Provides evidence that self-antigens can be cross-presented and that this leads to deletional tolerance. |
10.4049/jimmunol.166.9.5327 | 19,834,207 | Abstract Mouse spleen contains three distinct mature dendritic cell (DC) populations (CD4+8−, CD4−8−, and CD4−8+) which retain a capacity to take up particulate and soluble Ags. Although the three splenic DC subtypes showed similar uptake of injected soluble OVA, they differed markedly in their capacity to present this... | 10.1038/35100512 | Provides evidence that CD8 + dendritic cells (DCs) are responsible for cross-presentation of soluble ovalbumin. It also shows that CD8 − CD4 − DCs can cross-present when exposed to lipopolysaccharide. |
10.1084/jem.192.12.1685 | 125,254,170 | Bone marrow–derived antigen-presenting cells (APCs) take up cell-associated antigens and present them in the context of major histocompatibility complex (MHC) class I molecules to CD8+ T cells in a process referred to as cross-priming. Cross-priming is essential for the induction of CD8+ T cell responses directed towar... | 10.1038/35100512 | The first report to show that CD8 + dendritic cells cross-present cell-associated antigens. |
10.1084/jem.184.3.923 | 82,871,019 | Ovalbumin (OVA)-specific CD8+ T cells from the T cell receptor-transgenic line OT-I (OT-I cells) were injected into unirradiated transgenic RIP-mOVA mice, which express a membrane-bound form of OVA (mOVA) in the pancreatic islet beta cells and the renal proximal tubular cells. OT-I cells accumulated in the draining lym... | 10.1038/35100512 | First paper to report cross-presentation of tissue antigens and showed this process is constitutive. |
10.1084/jem.188.2.409 | 38,571,454 | Naive T cells recirculate mainly within the secondary lymphoid compartment, but once activated they can enter peripheral tissues and perform effector functions. To activate naive T cells, foreign antigens must traffic from the site of infection to the draining lymph nodes, where they can be presented by professional an... | 10.1038/35100512 | Provides the important observation that antigen dose is vital to whether a tissue antigen will be cross-presented. Also shows that tissue damage enhances cross-presentaton. |
10.1084/jem.191.3.435 | 83,484,247 | This study identifies a dendritic cell (DC) subset that constitutively transports apoptotic intestinal epithelial cell remnants to T cell areas of mesenteric lymph nodes in vivo. Rat intestinal lymph contains two DC populations. Both populations have typical DC morphology, are major histocompatibility complex class IIh... | 10.1038/35100512 | Shows that gut-associated dendritic cells constitutively capture apoptotic epithelial cells and transport them to the mesenteric lymph node. |
10.4049/jimmunol.166.6.3717 | 102,095,670 | Abstract Dendritic cells (DC) can readily capture Ag from dead and dying cells for presentation to MHC class I-restricted CTL. We now show by using a primate model that DC also acquire Ag from healthy cells, including other DC. Coculture assays showed that fluorescently labeled plasma membrane was rapidly and efficient... | 10.1038/35100512 | First paper to show that dendritic cells might capture and cross-present antigens from other cells without killing the donor cells. |
10.1073/pnas.92.21.9465 | 103,907,015 | In this paper we report a recessive mutation, immune deficiency (imd), that impairs the inducibility of all genes encoding antibacterial peptides during the immune response of Drosophila. When challenged with bacteria, flies carrying this mutation show a lower survival rate than wild-type flies. We also report that, in... | 10.1038/35066006 | This paper showed for the first time that immune signalling in Drosophila proceeds by more than one pathway. |
10.1126/science.285.5435.1917 | 81,210,875 | The antifungal defense of Drosophila is controlled by the spaetzle/Toll/cactus gene cassette. Here, a loss-of-function mutation in the gene encoding a blood serine protease inhibitor, Spn43Ac, was shown to lead to constitutive expression of the antifungal peptide drosomycin, and this effect was mediated by the spaetzle... | 10.1038/35066006 | This paper shows that Spätzle is the Toll ligand in the immune response, and highlights the issue of immune recognition by pattern receptors and/or other proteins. |
10.1126/science.282.5396.2085 | 125,063,695 | Mutations of the gene Lps selectively impede lipopolysaccharide (LPS) signal transduction in C3H/HeJ and C57BL/10ScCr mice, rendering them resistant to endotoxin yet highly susceptible to Gram-negative infection. The codominant Lps d allele of C3H/HeJ mice was shown to correspond to a missense mutation in the third exo... | 10.1038/35066006 | Positional cloning of the Lipopolysaccharide ( Lps ) gene in mice revealed that Tlr4 is the long-sought signalling chain of the mammalian endotoxin receptor. This permitted the first assignment of a specific function to a Toll-like receptor in mammals. |
10.1126/science.287.5461.2204 | 62,616,040 | A comparative analysis of the genomes of Drosophila melanogaster , Caenorhabditis elegans , and Saccharomyces cerevisiae —and the proteins they are predicted to encode—was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in si... | 10.1038/35066006 | The comparison of the Drosophila genome sequence with the human genome sequence made in this paper and in reference 13 reveals new information and possibilities related to immunity. |
10.1093/embo-reports/kvd073 | 122,560,560 | The Drosophila innate immune system discriminates between pathogens and responds by inducing the expression of specific antimicrobial peptide‐encoding genes through distinct signaling cascades. Fungal infection activates NF‐κB‐like transcription factors via the Toll pathway, which also regulates innate immune responses... | 10.1038/35066006 | With reference 91 this paper shows that a caspase is involved in Drosophila immunity, and advances the connections between immunity and apoptosis. |
10.1073/pnas.95.2.652 | 16,746,483 | Effective tumor immunity requires recognition of tumor cells coupled with the activation of host effector responses. Fc receptor (FcR) γ −/− mice, which lack the activating FcγR types I and III, did not demonstrate protective tumor immunity in models of passive and active immunization against a relevant tumor different... | 10.1038/35101072 | First demonstration that the antitumour activity of an antibody can be critically dependent on interaction between its Fc region and Fcγ receptors. Similar findings have subsequently been made with several other antibodies, including the clinically important Herceptin and Rituxan (reference 32 |
10.1073/pnas.93.16.8618 | 84,352,046 | The maytansinoid drug DM1 is 100- to 1000-fold more cytotoxic than anticancer drugs that are currently in clinical use. The immunoconjugate C242-DM1 was prepared by conjugating DM1 to the monoclonal antibody C242, which recognizes a mucin-type glycoprotein expressed to various extents by human colorectal cancers. C242-... | 10.1038/35101072 | Compelling demonstration of the in vivo antitumour efficacy of an antibody armed with maystansine, even against tumours that are very large or heterogeneous in antigen expression. |
10.1073/pnas.131187998 | 44,855,669 | Effective chemotherapy remains a key issue for successful cancer treatment in general and neuroblastoma in particular. Here we report a chemotherapeutic strategy based on catalytic antibody-mediated prodrug activation. To study this approach in an animal model of neuroblastoma, we have synthesized prodrugs of etoposide... | 10.1038/35101072 | Important milestone on the road to developing a catalytic antibody for targeted prodrug therapy. |
10.1073/pnas.90.19.8996 | 18,797,761 | Antibody-based therapy of solid tumors has met with limited success, chiefly because solid tumors are relatively impermeable to macromolecules. This problem could be circumvented by attacking the readily accessible endothelial cells of the tumor vascular bed. We have developed a model to test this "vascular targeting" ... | 10.1038/35101072 | Shows the antitumour activity of an immunotoxin that targets tumour vasculature. The greatest efficacy is achieved by combining this immunotoxin with one that directly targets the tumour. |
10.1083/jcb.152.5.1079 | 28,022,197 | Caveolin-1 and -2 constitute a framework of caveolae in nonmuscle cells. In the present study, we showed that caveolin-2, especially its β isoform, is targeted to the surface of lipid droplets (LD) by immunofluorescence and immunoelectron microscopy, and by subcellular fractionation. Brefeldin A treatment induced furth... | 10.1038/35089558 | References 29 and 30 describe the discovery of new membrane domains in cells, and their association with caveolin. Great morphological studies and excellent time-lapse microscopy. |
10.1126/science.290.5500.2298 | 38,209,845 | Niemann-Pick type C2 disease (NP-C2) is a fatal hereditary disorder of unknown etiology characterized by defective egress of cholesterol from lysosomes. Here we show that the disease is caused by a deficiency in HE1, a ubiquitously expressed lysosomal protein identified previously as a cholesterol-binding protein. HE1 ... | 10.1038/35089558 | Elucidation of the molecular defect in NPC type 2 disease. |
10.1126/science.274.5285.255 | 82,811,098 | Hedgehog (Hh) proteins comprise a family of secreted signaling molecules essential for patterning a variety of structures in animal embryogenesis. During biosynthesis, Hh undergoes an autocleavage reaction, mediated by its carboxyl-terminal domain, that produces a lipid-modified amino-terminal fragment responsible for ... | 10.1038/35089558 | An excellent paper, demonstrating the autoproteolysis and cholesterol modification of Hedghog protein. |
10.1073/pnas.92.9.3869 | 102,720,270 | Most helicases studied to date have been characterized as oligomeric, but the relation between their structure and function has not been understood. The bacteriophage T7 gene 4 helicase/primase proteins act in T7 DNA replication. We have used electron microscopy, three-dimensional reconstruction, and protein crosslinki... | 10.1038/35036044 | The electron-microscope (EM) structure of a replicative hexameric DNA helicase provided insights into how these enzymes form a ring that encircles single-stranded DNA and catalyse unwinding of duplex DNA. |
10.1073/pnas.94.10.5012 | 122,095,364 | Bacteriophage T7 DNA helicase is a ring-shaped hexamer that catalyzes duplex DNA unwinding using dTTP hydrolysis as an energy source. Of the six potential nucleotide binding sites on the hexamer, we have found that three are noncatalytic sites and three are catalytic sites. The noncatalytic sites bind nucleotides with ... | 10.1038/35036044 | Rapid kinetic analysis of the NTPase activity of a hexameric helicase yielded a model mechanism for helicase-catalysed sequential TTP hydrolysis (similar to F 1 -ATPase) that may be coupled to stepwise DNA unwinding. |
10.1073/pnas.96.19.10684 | 79,469,225 | The bacterial RecA protein has been the most intensively studied enzyme in homologous genetic recombination. The core of RecA is structurally homologous to that of the F1-ATPase and helicases. Like the F1-ATPase and ring helicases, RecA forms a hexameric ring. The human Dmc1 (hDmc1) protein, a meiosis-specific recombin... | 10.1038/35036044 | EM structure of this ring-shaped human RecA homologue opens up new possible mechanisms of action of RecA-like proteins in homologous recombination or other metabolic processes. |
10.1126/science.279.5356.1534 | 122,970,220 | The three-dimensional structure of a 70-kilodalton amino terminally truncated form of human topoisomerase I in complex with a 22–base pair duplex oligonucleotide, determined to a resolution of 2.8 angstroms, reveals all of the structural elements of the enzyme that contact DNA. The linker region that connects the centr... | 10.1038/35036044 | The series of crystal structures of human topoisomerase I in references 68 and 69 provide detailed snapshots of the process by which this enzyme catalyses changes in the topology of DNA. |
10.1073/pnas.96.24.13685 | 16,746,417 | DNA topoisomerase II is a homodimeric molecular machine that couples ATP usage to the transport of one DNA segment through a transient break in another segment. In the presence of a nonhydrolyzable ATP analog, the enzyme is known to promote a single turnover of DNA transport. Current models for the enzyme’s mechanism b... | 10.1038/35036044 | A rapid kinetic study of the topoisomerase II reaction yields a model mechanism by which this enzyme couples ATP binding and hydrolysis to catenation or decatenation of duplex DNA. |
10.1101/gr.10.7.991 | 1,655,469 | Accumulation of complete genome sequences of diverse organisms creates new possibilities for evolutionary inferences from whole-genome comparisons. In the present study, we analyze the distributions of substitution rates among proteins encoded in 19 complete genomes (the interprotein rate distribution). To estimate the... | 10.1038/35036044 | A comprehensive phylogenetic and structural analysis of RecA-like proteins and the DnaB family of hexameric helicases indicates that these proteins share a common ancestor that had the ability to form oligomeric rings and undergo NTP-driven conformational changes. |
10.1073/pnas.96.11.6307 | 123,179,975 | SMN1 and SMN2 (survival motor neuron) encode identical proteins. A critical question is why only the homozygous loss of SMN1 , and not SMN2 , results in spinal muscular atrophy (SMA). Analysis of transcripts from SMN1/SMN2 hybrid genes and a new SMN1 mutation showed a direct relationship between presence of disease and... | 10.1038/35049061 | Systematic study of the nucleotides that differ between SMN1 and SMN2 , which shows that a single nucleotide exchange attenuates the activity of an exonic splicing enhancer. |
10.1126/science.280.5364.737 | 27,008,332 | Myotonic dystrophy (DM) is caused by a CTG expansion in the 3′ untranslated region of the DM gene. One model of DM pathogenesis suggests that RNAs from the expanded allele create a gain-of-function mutation by the inappropriate binding of proteins to the CUG repeats. Data presented here indicate that the conserved hete... | 10.1038/35049061 | Evidence that CUG repeats associated with myotonic dystrophy might disrupt regulation of alternative splicing through interactions with CUG-binding protein. |
10.1128/mcb.17.8.4667 | 103,572,483 | The neural cell-specific N1 exon of the c-src pre-mRNA is both negatively regulated in nonneural cells and positively regulated in neurons. We previously identified conserved intronic elements flanking N1 that direct the repression of N1 splicing in a nonneural HeLa cell extract. The upstream repressor elements are loc... | 10.1038/35049061 | The polypyrimidine-tract-binding protein represses neuron-specific splicing of c-src through interaction with an upstream sequence element in non-neuronal cells. |
10.1073/pnas.110128397 | 17,779,346 | The Nova paraneoplastic antigens are neuron-specific RNA binding proteins that participate in the control of alternative splicing. We have used the yeast two-hybrid system to isolate Nova interacting proteins and identify an RNA binding protein that is closely related to the polypyrimidine tract-binding protein (PTB). ... | 10.1038/35049061 | Cloning and identification of brain-enriched polypyrimidine-tract-binding protein and evidence for a role in the regulation of alternative splicing in neurons through interactions with NOVA. |
10.1073/pnas.95.18.10419 | 100,815,849 | Eukaryotic translation initiation factor 5A (eIF-5A) is a ubiquitous protein found in all eukaryotic cells. The protein is closely associated with cell proliferation in the G 1 –S stage of the cell cycle. Recent findings show that the eIF-5A proteins are highly expressed in tumor cells and act as a cofactor of the Rev ... | 10.1038/35093574 | A report of one of the first structural genomics proteins solved; it represented inadvertent duplication of effort, as the same structure was independently solved in the next reference. |
10.1126/science.286.5447.2119 | 83,411,433 | Tubby-like proteins (TULPs) are found in a broad range of multicellular organisms. In mammals, genetic mutation of tubby or other TULPs can result in one or more of three disease phenotypes: obesity (from which the name “tubby” is derived), retinal degeneration, and hearing loss. These disease phenotypes indicate a vit... | 10.1038/35093574 | This paper predicts the DNA-binding function of tubby proteins on the basis of examination of the surface electrostatics of the structure. |
10.1073/pnas.95.26.15189 | 122,095,381 | Many small bacterial, archaebacterial, and eukaryotic genomes have been sequenced, and the larger eukaryotic genomes are predicted to be completely sequenced within the next decade. In all genomes sequenced to date, a large portion of these organisms’ predicted protein coding regions encode polypeptides of unknown bioc... | 10.1038/35093574 | This paper reports that a bound ATP that was found in the solved structure indicated that this hypothetical protein is a molecular switch. |
10.1073/pnas.090099097 | 102,575,023 | We have used intramolecular cross-linking, MS, and sequence threading to rapidly identify the fold of a model protein, bovine basic fibroblast growth factor (FGF)-2. Its tertiary structure was probed with a lysine-specific cross-linking agent, bis(sulfosuccinimidyl) suberate (BS 3 ). Sites of cross-linking were determi... | 10.1038/35093574 | In this work, cross-linking and mass spectrometry were used to glean limited structural information, sufficient to predict a protein fold. |
10.1126/science.280.5371.1940 | 60,522,194 | Long-term potentiation (LTP) at the Schaffer collateral–CA1 synapse involves interacting signaling components, including calcium (Ca 2+ )/calmodulin–dependent protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) pathways. Postsynaptic injection of thiophosphorylated inhibitor-1 protein, a specific inhib... | 10.1038/35081514 | An example of how complex regulatory mechanisms govern phosphorylation and dephosphorylation in the induction of LTP. |
10.1126/science.285.5424.93 | 104,168,320 | Regulation of N -methyl- d -aspartate (NMDA) receptor activity by kinases and phosphatases contributes to the modulation of synaptic transmission. Targeting of these enzymes near the substrate is proposed to enhance phosphorylation-dependent modulation. Yotiao, an NMDA receptor–associated protein, bound the type I prot... | 10.1038/35081514 | An illustration of the role of postsynaptic supramolecular complexes in the regulation of receptor function. |
10.1046/j.1471-4159.2000.740807.x | 125,045,622 | Abstract: Using autophosphorylated Ca 2+ /calmodulin‐dependent protein kinase II (CaM kinase II) as substrate, we now find that long‐term potentian (LTP) induction and maintenance are also associated with a significant decrease in calyculin A‐sensitive protein phosphatase (protein phosphatase 2A) activity, without chan... | 10.1038/35081514 | References 64 and 75 are two of the few studies directly assessing protein phosphatase activity in synaptic plasticity. |
10.1101/gr.160601 | 59,319,478 | The maize genome contains extensive chromosomal duplications that probably were produced by an ancient tetraploid event. Comparative cereal maps have identified at least 10 duplicated, or homologous, chromosomal regions within maize. However, the methods used to document chromosomal homologies from comparative maps are... | 10.1038/35072009 | Interesting exploration of methods for statistically testing genome duplication hypotheses. |
10.1126/science.290.5494.1151 | 41,673,779 | Gene duplication has generally been viewed as a necessary source of material for the origin of evolutionary novelties, but it is unclear how often gene duplicates arise and how frequently they evolve new functions. Observations from the genomic databases for several eukaryotic species suggest that duplicate genes arise... | 10.1038/35072009 | Global study of the frequency of occurrence and degree of divergence of duplicated genes in several eukaryotic genomes. This paper shows that duplicated genes arise at a high rate but have a short half-life. |
10.1073/pnas.96.26.15173 | 79,469,152 | On the causal hypothesis, most genetic determinants of disease are single-nucleotide polymorphisms (SNPs) that are likely to be selected as markers for positional cloning. On the proximity hypothesis, most disease determinants will not be included among markers but may be detected through linkage disequilibrium with ot... | 10.1038/35052543 | One of a series of key papers by these authors who compare disequilibrium measures, evaluate real data patterns to infer genome-wide marker spacing requirements, and combine population genetics principles with those of disease-gene mapping to characterize allelic association. |
10.1038/npg.els.0005429 | 65,026,425 | Abstract Genes that contribute to complex genetic diseases can sometimes be identified by studies that show genetic linkage, or association, with marker genes. The transmission/disequilibrium test is a procedure that tests for the simultaneous presence of these two genetic phenomena. | 10.1038/35052543 | The TDT test and its immediate predecessors changed the way human genetic studies were conducted throughout the past decade. This is the original paper describing the method |
10.1126/science.287.5452.501 | 104,325,817 | Although ubiquitinated histones are present in substantial levels in vertebrate cells, the roles they play in specific biological processes and the cellular factors that regulate this modification are not well characterized. Ubiquitinated H2B (uH2B) has been identified in the yeast Saccharomyces cerevisiae , and mutati... | 10.1038/35056583 | Although histones H2A and H2B were known to be monoubiquitylated for more than two decades, this paper provided the first evidence that histone ubiquitylation was important for function. Yeast mutants that cannot ubiquitylate histone H2B grow more slowly than wild-type cells and do not sporulate. |
10.1126/science.289.5488.2357 | 81,411,055 | Ubiquitination of histones has been linked to the complex processes that regulate the activation of eukaryotic transcription. However, the cellular factors that interpose this histone modification during the processes of transcriptional activation are not well characterized. A biochemical approach identified the Drosop... | 10.1038/35056583 | Drosophila histone H1 is monoubiquitylated by TAF250, an unusual multifunctional protein that seems to carry E1 and E2 activities in the same polypeptide. TAF250 ubiquitylation of H1 seems to be important for the proper regulation of transcriptional activity in Drosophila embryos. |
10.1073/pnas.97.24.13063 | 20,624,054 | Retroviral Gag polyproteins have specific regions, commonly referred to as late assembly (L) domains, which are required for the efficient separation of assembled virions from the host cell. The L domain of HIV-1 is in the C-terminal p6 gag domain and contains an essential P(T/S)AP core motif that is widely conserved a... | 10.1038/35056583 | This paper shows that ubiquitin is important for virus budding and brings ubiquitin protein ligases into the picture. The proline-rich motifs in viral L domains that mediate interaction with ubiquitin protein ligases are required for Gag ubiquitylation and virus budding. |
10.1073/pnas.97.24.13069 | 40,355,510 | Retroviruses contain relatively large amounts of ubiquitin, but the significance of this finding has been unknown. Here, we show that drugs that are known to reduce the level of free ubiquitin in the cell dramatically reduced the release of Rous sarcoma virus, an avian retrovirus. This effect was suppressed by overexpr... | 10.1038/35056583 | Depletion of intracellular ubiquitin levels inhibits virus budding at a late stage and this defect can be partially restored by fusing ubiquitin in-frame to Gag. This provides evidence that ubiquitylation of Gag is required for release of virus particles from the host cell. |
10.1126/science.290.5496.1582 | 84,385,265 | An enduring controversy in neuroscience concerns how the brain “binds” together separately coded stimulus features to form unitary representations of objects. Recent evidence has indicated a close link between this binding process and 40-hertz (gamma-band) oscillations generated by localized neural circuits. In a separ... | 10.1038/35081509 | The first demonstration of task-related 'bursts' of neural oscillations in human infants of 8 months. These oscillatory bursts correspond to the ability of the brain to 'bind' spatially separate features into a new single object and provide a direct measure of infants' ability to process objects. |
10.1111/1467-9280.00024 | 62,436,871 | Two experiments examined whether infants shift their visual attention in the direction toward which an adult's eyes turn. A computerized modification of previous joint-attention paradigms revealed that infants as young as 3 months attend in the same direction as the eyes of a digitized adult face. This attention shift ... | 10.1038/35081509 | An important link between research on attentional cueing in young babies, and work on social cognition and joint attention. Shows that the attention of young infants can be cued to a target location by the direction of eye gaze of a realistic face. |
10.1126/science.286.5437.108 | 18,658,446 | Visual acuity was assessed in 28 human infants who had been deprived of all patterned visual input by cataracts in one or both eyes until they were treated at 1 week to 9 months of age. Immediately after treatment, acuity was no better than that of normal newborns. Acuity improved significantly over the next month, wit... | 10.1038/35081509 | A study with patients visually deprived over the first months or years of life owing to cataracts. The improvements in acuity following corrective surgery were surprisingly rapid, although some degree of deficit remained even after years of restored vision. |
10.1126/science.286.5448.2355 | 79,744,008 | This study challenges the use of adult neuropsychological models for explaining developmental disorders of genetic origin. When uneven cognitive profiles are found in childhood or adulthood, it is assumed that such phenotypic outcomes characterize infant starting states, and it has been claimed that modules subserving ... | 10.1038/35081509 | A study that investigated whether the profiles of cognitive abilities and disabilities observed in adults with developmental disorders are also observed during infancy. The results show that profiles of cognitive disability might change during development. |
10.1126/science.287.5452.482 | 62,514,994 | Acidic media trigger cytoplasmic urease activity of the unique human gastric pathogen Helicobacter pylori. Deletion of ureI prevents this activation of cytoplasmic urease that is essential for bacterial acid resistance. UreI is an inner membrane protein with six transmembrane segments as shown by in vitro transcription... | 10.1038/35073084 | A remarkable paper on how this bacterium handles the vital urea molecule. |
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