Evidence for an early regulatory function in phage P22

Summary A temperature sensitive mutant of P22 phage (ts X) was isolated and studied.This mutant seems to have a basic regulatory function: it is defective in an early function like the typical DNA^- mutant ts 12.1; it is unable to direct the phage DNA synthesis and does not lyse infected or induced cells.Unlike ts 12.1, the mutation ts X seems to involve a gene product necessary for the expression of any vegetative function, since no phage protein synthesis, no alteration of host DNA synthesis, and no cell killing can be observed under non-permissive conditions.The possible functional similarity between the N-cistron of the phage and the present X-cistron in P22 is discussed.     

Evidence for an early free radical-mediated reperfusion injury in frostbite

Frostbite is characterized by acute tissue injury induced by freezing and thawing. Initial complete ischemia is followed by reperfusion and later, tissue necrosis. These vascular events support the hypothesis that free radical-mediated reperfusion injury at thawing might contribute to tissue necrosis after frostbite in a manner similar to that seen after normothermic ischemia. To test this hypothesis, rabbit ears were frozen at -21 degrees C for 30, 60, 90, or 120 s and rewarmed at room temperature (22 degrees C). Rabbits were treated "blindly" with saline alone, highly purified, pharmaceutical grade superoxide dismutase (SOD), allopurinol, or deferoxamine. The area of ear necrosis was determined 3 weeks after frostbite by "blinded" morphometry. The administration of SOD at the time of thawing significantly improved viability in ears frozen for 60 and 90 s, but not in those frozen for 30 or 120 s. Deferoxamine also improved viability in ears frozen for 60 s. Allopurinol did not significantly affect ear survival. Electron micrographs showed the appearance of severe endothelial cell injury beginning during freezing and extending through early reperfusion. Later, neutrophil adhesion, erythrocyte aggregation, and microvascular stasis were seen. These findings suggest that free radical-mediated reperfusion injury has a role in frostbite, and quantitate the proportion of the injury that is due to this mechanism.     

Evidence for social role in a dolphin social network

Social animals have to take into consideration the behaviour of conspecifics when making decisions to go by their daily lives. These decisions affect their fitness and there is therefore an evolutionary pressure to try making the right choices. In many instances individuals will make their own choices and the behaviour of the group will be a democratic integration of everyone’s decision. However, in some instances it can be advantageous to follow the choice of a few individuals in the group if they have more information regarding the situation that has arisen. Here I provide early evidence that decisions about shifts in activity states in a population of bottlenose dolphin follow such a decision-making process. This unshared consensus is mediated by a non-vocal signal, which can be communicated globally within the dolphin school. These signals are emitted by individuals that tend to have more information about the behaviour of potential competitors because of their position in the social network. I hypothesise that this decision-making process emerged from the social structure of the population and the need to maintain mixed-sex schools.     

Class discourse in an early 19th-century New England factory

Conclusions While the egalitarian, Republican ring of the 1833 exchange of speeches between Collins and his workers was not a true reflection of the relationship between them, it held sufficient mutual beliefs and desires to be spoken and heard as meaningful. By 1846 the edge of class had sharpened, and language was no longer able to dull it. The speech in 1846 was not successful. There is no record of the workers' language since Collins did not record either their request nor their response—although he copied his own excessively long speech into his memoirs—but we have Collins's word that the speech was not effective, and the men began to leave. According to Collins, in 1846 the circumstances and the men were different.⁶⁵ He might have added that he, also, was different, but it was a statement of the increasing distance between the classes that had not been bridged by the acceptance of hegemonic discourse.According to Wilentz, the shift from Republicanism to a liberal rhetoric of supply and demand was equally unconvincing to New York artisans of this period. While the masters argued that the price of all commodities including labor...were not governed by an engrossing or monopolizing spirit on the part of the landowners or employers but by the limits of supply and demand;⁶⁶ the journeymen argued that the masters' plea that they only followed the laws of supply and demand was a fraudulent ruse, an impudent denial of the best motives of the Revolution and the Constitution.⁶⁷ In fact, this early use of the ideology of independence of the market coincided with an unprecedented involvement of government into the economy.⁶⁸ For the entrepreneurs who invested in and developed the new industries, Republicanism had been an adequate language for surrounding their actions with a patriotic gloss as they gained governmental and public support—financial, legal, and ideological—for private development and profit. It covered class divisions with a cloak of unity. However, the language of Republicanism was potentially inflammatory for workers as well as limiting to the business classes. At Lowell, in 1834, the striking women had circulated a petition grandly composed in Republicanism's rhetoric to protest the tyranny of the workplace: Our present object is to have union and exertion, and we remain in possession of our unquestionable rights. We circulate this paper wishing to obtain the names of all who imbible the spirit of our Patriotic Ancestors, who preferred privation to bondage, and parted with all that renders life desirable and even life itself to procure independence for their children.⁶⁹ Wilentz traces the development of Republicanism in the protests of the New York artisans, who argued that only the journeymen, had the right to judge the value of their labor,⁷⁰ and, even as late as 1850, battled not only specific wages but the wages system itself.⁷¹ At the Collins Company as elsewhere, as management developed more control over labor it spoke a different language. Collins was to some degree restrained by his own prior constructs and experiences. Later generations of employers would have no problem publicly facing their employees and rationalizing exploitation with the bland violence of liberal individualism, telling them that supply and demand was a natural law, self-interest worked to the benefit of all, and since anyone who worked hard could succeed, failure was the fault of the individual. Democracy's place was outside of the workplace after working hours. It was guaranteed by public suffrage and the two-party system.For historians, the recent delineation of Republicanism has led to the understanding that liberal individualism is not just a natural American way to think but a cultural artifact whose beginnings can be traced. The impetus to understand and describe our own world view as a cultural fact has been the increasing inability of liberal individualism to explain or express the economic, social, and political world we live in. By 1846 the class division had become too strongly established for the language of Republicanism to meaningfully bridge it. By 1989 the same could be said for liberal individualism.     

Economic and social structure for an ageing population.

The driving force behind the improvement in the quality of life, the rising standard of living, improving health, and increasing longevity, is a process called ''technophysio evolution'', which began about 300 years ago, accelerated during the twentieth century, and is still in progress. Increased spending on health care and on pensions is an appropriate concomitant of technophysio evolution, and should be welcomed. Only wasteful medical services should be restricted. The resources available now and in the future can provide increasingly long and healthy lives of relative luxury for all. However, methods of financing health care and retirement need to be modernized. In the future, luxury will be defined increasingly in terms of spiritual rather than material resources. The test of well-being in the future for both young and old will be measured increasingly in terms of the quality of health and the opportunity for self-realization.     

Evidence for an early role for BMP4 signaling in thymus and parathyroid morphogenesis

The thymus and parathyroids are pharyngeal endoderm-derived organs that develop from common organ primordia, which undergo a series of morphological events resulting in separate organs in distinct locations in the embryo. Previous gene expression and functional analyses have suggested a role for BMP4 signaling in early thymus organogenesis. We have used conditional deletion of Bmp4 or Alk3 from the pharyngeal endoderm and/or the surrounding mesenchyme using Foxg1-Cre, Wnt1-Cre or Foxn1-Cre. Deleting Bmp4 from both neural crest cells (NCC) and early endoderm-derived epithelial cells in Foxg1-Cre;Bmp4 conditional mutants resulted in defects in thymus-parathyroid morphogenesis. Defects included reduced condensation of mesenchymal cells around the epithelium, partial absence of the thymic capsule, a delay in thymus and parathyroid separation, and failed or dramatically reduced organ migration. Patterning of the primordia and initial organ differentiation were not affected in any of the mutants. Deleting Bmp4 from NCC-derived mesenchyme or differentiating thymic epithelial cells (TECs) had no effects on thymus-parathyroid development, while loss of Alk3 from either neural crest cells or TECs resulted in only a mild thymic hypoplasia. these results show that the processes of cell specification and morphogenesis during thymus-parathyroid development are independently controlled, and suggest a specific temporal and spatial role for BMP4-mediated epithelial-mesenchymal interactions during early thymus and parathyroid morphogenesis.     

Allocating resources for health and social care in England.

The fair allocation of resources for health and social care in relation to the needs of the population in different parts of the United Kingdom has become particularly important since the implementation of the new arrangements for community care in April 1993. These depend on close collaboration between health authorities and local authority social services departments. Yet funding reaches these authorities by different means and according to different criteria. Most health authority funds come through a weighted capitation formula that overemphasises the effects of age, while family health services funding is largely not cash limited and hence demand led. Funds to local authorities for community care are being transferred from the social security budget but on a basis that partly reflects past provision of residential and nursing home care. None of these mechanisms responds to underlying needs that give rise to demands on the health and social care system as a whole, and none makes any attempt to compensate for defects in the others. The solution includes better research and a unified weighted capitation system for all sources of funding.     

Evidence for specificity at an early step in protein export in Escherichia coli.

We previously described mutations in a gene, secB, which have pleiotropic effects on protein export in Escherichia coli. In this paper, we report the isolation of mutants in which the activity of the secB gene was eliminated. Null mutations in secB affected only a subset of exported proteins. Strains carrying these mutations, although unable to grow on L broth plates, were still viable on minimal media. These secB mutations reversed a block in the translation of an exported protein that was caused by the elimination of another component of the secretion machinery, SecA protein. These results suggest that the secB product acts at an early step in the export process and is involved in the export of only a subset of cell envelope proteins.     

Evidence of amelogenesis imperfecta in an early African Homo erectus

The teeth of the Homo erectus child (Garba IV) recovered from Melka Kunture Ethiopia and dated to 1.5 Ma are characterized by generalized enamel dysplasia, reduced enamel radio-opacity, and severe attrition. This combination of features is found in a large group of hereditary, generalized enamel dysplasias known as amelogenesis imperfecta (AI). SEM studies carried out on epoxy replicas of teeth from the Garba IV child, confirmed that the defects noted were developmental and not due to diagenesis. The enamel prism arrangement is abnormal and there are deep vertical furrows lacking enamel on both buccal and lingual surfaces of all molars. The lesions differ from those characteristic of linear enamel hypoplasia that form discrete horizontal lesions or pits within otherwise normal enamel. We propose that the Garba IV child is the earliest example of AI and provides a link between palaeoanthropology and molecular biology in investigations of the evolutionary history of genetic disorders.     

Evidence for weak or linear conformity but not for hyper-conformity in an everyday social learning context

Conformity is thought to be an important force in cultural evolution because it has the potential to stabilize cooperation in large groups, potentiate group selection and thus explain uniquely human behaviors. However, the effects of such conformity on cultural and biological evolution will depend much on the way individuals are influenced by the frequency of alternative behavioral options witnessed. Theoretical modeling has suggested that only what we refer to as 'hyper-conformity', an exaggerated tendency to perform the most frequent behavior witnessed in other individuals, is able to increase within-group homogeneity and between-group diversity, for instance. Empirically however, few experiments have addressed how the frequency of behavior witnessed affects behavior. Accordingly we performed an experiment to test for the presence of conformity in a natural situation with humans. Visitors to a Zoo exhibit were invited to write or draw answers to questions on A5 cards and potentially win a small prize. We manipulated the proportion of existing writings versus drawings visible to visitors and measured the proportion of written cards submitted. We found a strong and significant effect of the proportion of text displayed on the proportion of text in the answers, thus demonstrating social learning. We show that this effect is approximately linear, with potentially a small, weak-conformist component but no hyper-conformist one. The present experiment therefore provides evidence for linear conformity in humans in a very natural context.     

Leaf malformation during early development in Sorghum. Evidence for an embryonic developmental window

Salt adaptation was induced in two successive generations of Sorghum bicolor , and the germination of their seeds was compared. When germinated in the absence of NaCl, the progeny of adapted plants displayed a specific malformation at the first two leaves, which was never observed in progeny of control plants. The frequency of leaf malformation was enhanced in progeny of the second generation of adapted plants, indicating a cumulative influence of salt adaptation. When germinated in the presence of 75 m M NaCl, seedlings from seeds of salt-adapted plants never displayed the leaf malformation, whereas it was observed on seedlings from seeds of control plants germinated in the presence of 75 m M NaCl. The occurrence of leaf malformation was analyzed for progeny of 20 salt-adapted plants germinated in the absence of NaCl. The link with the reproductive characters of the parents indicates a strong parental control on the expression of the leaf malformation. A comparison with previous data relative to the leaf malformation in Sorghum suggests the existence of a developmental window which 'opens'during embryo morphogenesis. This enables the imprinting of the embryo by the parent's physiological environment. This conclusion is related to other data describing a long-term maternal influence in plants.     

Inner-ear structure in Morganucodon, an early Jurassic mammal

The shapes and dimensions of the cochlear cavities from four petrosals of the genus Morganucoden obtained through sectioning and reconstruction. Morganucodon dates from the early Jurassic and represents many of the earliest known mammal specimens. Each Morganucodon petrosal fossil was embedded in Araldite and shaved with an ultramicrotome to expose the internal structure. Line drawings of the exposed cross-sections were digitized and used to produce three-dimensional reconstructions. The reconstructed Monganucodon cochlear cavities differ from extant mammalian cochleas in several respects: they are uncoiled, shorter in length, and lack the bony lamina which supports the basilar membrane. These three features ar characteristic of extant Aves and Reptilia.     

Evidence for early disease-modifying drugs in rheumatoid arthritis

Some research evidence supports early aggressive treatment of rheumatoid arthritis (RA) using combination therapy with two or more disease modifying anti-rheumatic drugs (DMARDs) plus steroids, or even DMARDs plus an anti-TNF. By contrast, conservatively delayed DMARD monotherapy, given after non-steroidal anti-inflammatory drugs have failed, has been criticised. However, recent long-term studies highlight the complexities in evaluating whether to abandon pyramidal treatment in favour of early DMARDs. Although patients given early DMARD therapy show short-term benefits, longer-term results show no prolonged clinical advantages from early DMARDs. By 5 years patients receiving early DMARDs had similar disease activity and comparable health assessment questionnaire scores to patients who received DMARDs later in their disease course. X-ray progression was persistent and virtually identical in both groups. These negative findings do not invalidate the case for early DMARD therapy, as it is gives sustained reductions in disease activity in the early years of treatment without excessive risks from adverse effects. However, early DMARDs alone do not adequately control RA in the longer term. This may require starting with very aggressive therapy or treating patients more aggressively after early DMARD therapy has been initiated.     

Evidence for early disease-modifying drugs in rheumatoid arthritis

Some research evidence supports early aggressive treatment of rheumatoid arthritis (RA) using combination therapy with two or more disease modifying anti-rheumatic drugs (DMARDs) plus steroids, or even DMARDs plus an anti-TNF. By contrast, conservatively delayed DMARD monotherapy, given after non-steroidal anti-inflammatory drugs have failed, has been criticised. However, recent long-term studies highlight the complexities in evaluating whether to abandon pyramidal treatment in favour of early DMARDs. Although patients given early DMARD therapy show short-term benefits, longer-term results show no prolonged clinical advantages from early DMARDs. By 5 years patients receiving early DMARDs had similar disease activity and comparable health assessment questionnaire scores to patients who received DMARDs later in their disease course. X-ray progression was persistent and virtually identical in both groups. These negative findings do not invalidate the case for early DMARD therapy, as it is gives sustained reductions in disease activity in the early years of treatment without excessive risks from adverse effects. However, early DMARDs alone do not adequately control RA in the longer term. This may require starting with very aggressive therapy or treating patients more aggressively after early DMARD therapy has been initiated.     

Evidence for an elongated dimeric structure of heparin-binding hemagglutinin from Mycobacterium tuberculosis

Heparin-binding hemagglutinin (HBHA) is a virulence factor of tuberculosis which is responsible for extrapulmonary dissemination of this disease. A thorough biochemical characterization of HBHA has provided experimental evidence of a coiled-coil nature of HBHA. These data, together with the low-resolution structures of a full-length form and a truncated form of HBHA obtained by small-angle X-ray scattering, have unambiguously indicated that HBHA has a dimeric structure with an elongated shape.     

Evidence for an ancestral core structure in nucleotide-binding proteins with the type A motif

Many proteins that bind purine nucleotide triphosphates have a type A sequence motif. Only two classes of structures for such proteins are so far available from X-ray crystallography. We examined the tertiary structures of representatives of the two classes, porcine cytoplasmic adenylate kinase and Escherichia coli translational elongation factor Tu. Comparison of the two proteins suggests that the A motif may be just one part of a larger common core structure consisting of four parallel strands of beta-sheet sandwiched between four alpha-helices. This compact core structure comprises over one half of each protein. We speculate that A motif proteins have diverged from a common ancestor having this core structure.     

Evidence for an extended 7SL RNA structure in the signal recognition particle.

The signal recognition particle (SRP) functions in conjunction with the SRP receptor to target nascent ectoplasmic proteins to the protein translocation machinery of the endoplasmic reticulum membrane. SRP is a ribonucleoprotein consisting of six distinct polypeptides and one molecule of 7SL RNA 300 nucleotides long. SRP has previously been visualized by a variety of electron microscopic techniques as a rod-shaped particle 24 nm long and 6 nm wide. We report here microanalysis by electron spectroscopic imaging which localizes the RNA molecule in SRP to primarily the two ends of the particle. These results suggest that the single 7SL RNA molecule spans the length of the particle. Micrographs from a scanning transmission electron microscope permit visualization of unstained SRP with low electron exposure, as well as the direct measurement of the mol. wt of the particle. These micrographs confirm our earlier suggestion that SRP is divided into three structural domains and allow discrimination of the two ends of the structure. The results of both techniques have been combined in a model for the structure of SRP in which we propose the basic orientation of the 7SL RNA. The structure proposed is consistent with the secondary structure predicted for the RNA and with biochemical data.