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Kru¨ppel-associated box (KRAB) domain-containing zinc finger proteins (KZFPs) are one of the largest groups of transcription factors encoded by tetrapods, with 378 members in human alone. KZFP genes are often grouped in clusters reflecting amplification by gene and segment duplication since the gene family first emerged more than 400 million years ago. Previous work has revealed that many KZFPs recognize transposable element (TE)-embedded sequences as genomic targets, and that KZFPs facilitate the co-option of the regulatory potential of TEs for the benefit of the host. Here, we present a comprehensive survey of the genetic features and genomic targets of human KZFPs, notably completing past analyses by adding data on close to a hundred family members. General principles emerge from our study of the TE-KZFP regulatory system, which point to multipronged evolutionary mechanisms underlaid by highly complex and combinatorial modes of action with strong influences on human speciation.

AbstractPope Celestine III (1191–98) condemned both truces and alliances between Christian and Muslim rulers in the Iberian Peninsula, but Innocent III (1198–1216) was more ready to allow and even encourage truces. Papal action was influenced by various factors. The popes’ interventions were dependent on the receipt of reports and petitions from the Peninsula, and Spanish rulers sought to manipulate the papacy in order to achieve their own ends. The two popes also had different crusading priorities. These matters do not, however, fully explain their differing approach. Innocent was more of a pragmatist than his predecessor, and was possibly also influenced by the views of decretists. Yet a more wide-ranging study, which takes account of varying circumstances, is needed before generalisations can be made about papal attitudes to truces and alliances with non-Christians.

In the Aragonese province of the Templars, as elsewhere in the West, it was the practice for brothers to be placed in charge of sections of a convent’s lands, thus creating sub-commanderies. Those appointed usually held office for only short terms and were usually brother sergeants. But there was no attempt to establish a uniform system: some convents had many more sub-commanderies than others; some sub-commanderies had only a brief existence, while others can be traced over long periods; the buildings in which they were based varied widely (only a few had chapels), as did the numbers of brothers and non-Templars residing in them; and the powers exercised by sub-commanders appear not always to have been the same.

Nucleotide metabolism has been targeted for many years and in various clinical settings, including cancer. The increased knowledge of certain enzymes involved in this metabolism and associated cellular processes accumulated over the last few years, gives important information related to the druggability of certain proteins and the use of inhibitors for others. Here, we review recent data on such enzymes with a major interest in drug development, i.e. SAMHD1 and the proteins of the NUDIX family. These include information on their roles in cancer progression, correlations with clinical outcomes in cancer patients, and the development and study of enzymatic inhibitors.

Les maisons templières, normalement pourvues d’une grande salle, d’un dortoir et d’une chapelle, n’avaient en revanche ni salle capitulaire ni infirmerie. Elles abritaient le plus souvent quelques frères, pour la plupart occupés aux tâches domestiques ou à des activités agricoles. Le nombre des chambres particulières a eu tendance à augmenter. Il est difficile de discerner ce que fut la spiritualité des individus, mais on constate, en règle générale, le respect des observances religieuses. Pour diverses raisons les chapitres hebdomadaires n’étaient pas fréquentés par la totalité des frères. Les admissions dans l’ordre qui y étaient traitées ont laissé davantage de traces que l’activité judiciaire. Les infractions aux règlements, cependant, n’étaient pas rares. Les frères entretenaient des liens étroits avec la société, entre autres avec le personnel à leur service et avec les gens qui vivaient une vie semi-religieuse. Mais la participation à la vie conventuelle de ceux qui n’étaient pas Templiers était limitée. Ils étaient exclus des chapitres, et seuls quelques prêtres séculiers étaient admis dans les dortoirs des frères. Mais la fréquentation des réfectoires était forte, même à la table des frères, et les chapelles templières étaient couramment ouvertes aux gens de l’extérieur.

Abstract:The practice of diverting crusaders from one area of conflict to another can be traced back at least as far as the beginning of the twelfth century. Commuting of vows in this way was early recognized to be a papal prerogative and usually involved crusaders who had originally vowed to go to the Holy Land. In the twelfth century commutations occurred on only a few occasions, when steps were taken to divert crusaders to the Iberian Peninsula when it was under serious threat. Commutations became much more frequent in the first half of the thirteenth century and were used to provide manpower against Christians as well as infidels. At that time popes often took the initiative: Gregory IX was anxious to provide help for the Latin Empire of Constantinople and Innocent IV and his successors needed assistance against the Hohenstaufen. The papacy did not, however, coerce crusaders, and many refused to commute their vows. Criticism of commuting was voiced, although the redeeming of vows for money attracted greater opprobrium. Commuting became less common in the closing decades of the thirteenth century, but the reasons for this decline are not explained in the sources and can only be conjectured.

Dominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12.

AbstractThis article seeks to reassess Otto of Grandson’s crusading activities and his links with the Templars. Little is known about his participation in Prince Edward’s crusade in the early 1270s, but he went out to the East again in 1290, though not– as is frequently asserted– as the delegate of Edward I. He assisted in the defence of Acre before sailing to Cyprus. That he had a major role there in the election of James of Molay as Templar master is questionable. He also visited Armenia, but it is doubtful whether he went to Jerusalem during his stay in the East. His relations with the Templars after he had returned to the West also merit re-examination. He did not, as has sometimes been suggested, return to Armenia in the late 1290s, but he was on several occasions planning to return to the East in the early fourteenth century. On one occasion he set out, but was robbed in France. It was only in 1319, when he was over eighty, that he finally abandoned his intention of going again on crusade. He has sometimes been suggested as the author of the crusading treatisesVia ad Terram Sanctam andMemoria Terre Sancte, but a close examination of the texts gives little support to this contention.

Smith Woodward embarked on the production of a catalogue of fossil fishes half a century after Louis Agassiz began a similar exercise. These two palaeontological goliaths remain the only authorities who saw all relevant fossil fish material in all important collections. Between their works there was a substantial increase in the number of species recognized, reflecting the nineteenth-century passion for collecting, the rise of museums, as well as an acceptance that species change through time. Agassiz was working in pre-evolutionary days but Smith Woodward's view on fish diversity was strongly influenced by the theory of evolution and specifically the writings of Thomas Henry Huxley as well as those of Edward Drinker Cope and Ramsay Heatley Traquair and their ideas of grades of evolution. Many of Smith Woodward's generic and species descriptions survive today as his lasting legacy. Higher classification has changed considerably with new discoveries and differing methods of classification.

Outsourcing of customer and other services to developing countries is a significant aspect of global commercial activity, and an area of explosive employment growth in many locations, such as India and the Philippines. The present paper investigates what is meant by the term ‘quality’ and the language choices made by Customer Service Representatives (CSRs) in outbound credit collection calls. The data is based on a case study undertaken in a call centre in the Philippines. We focus specifically on an analysis of authentic calls and how the language choices relate to calls being assessed within the industry as ‘good’, ‘average’ and ‘poor’. The analysis of the transcribed data revealed that the speech functions and the choice of ‘Mood’ – i.e. whether a clause is a declarative, interrogative or imperative – were important features of the call, and that these choices were related to the assessment of calls being labelled as ‘good’ or ‘poor’ calls. An understanding of what a ‘good’ call looks like can help inform the quality assurance and training practices within the industry.

The early expansion of Islam led in time to widespread conversions of Christians in conquered territories. In the later eleventh century, however, western Christendom was in turn launching offensives against Islam on several fronts. Territorial gains were made in various Mediterranean regions and, although by the end of the thirteenth century the Holy Land had been lost again, Sicily remained in Christian hands, and in the second half of the thirteenth century in the Iberian peninsula only Granada remained under Muslim control: the whole peninsula was under Christian rule before the end of the fifteenth century. This expansion was accompanied, especially in the thirteenth century, by attempts to convert Muslims and other non-Christians. Yet in the period from the late eleventh until the later fifteenth century some western Christians converted to Islam. The purpose of the present paper is to consider the situations that prompted the adoption of Islam, and the reasons for such conversions, although the evidence is usually insufficient to indicate exactly why a particular Christian became a Muslim: the preconceived ideas voiced in western sources about forced conversions can be misleading and, although a crude distinction might be made between conversions from conviction and those based on worldly considerations, motives did not necessarily always fit neatly into just one of these two categories. But obviously not all converts would have had an equal understanding of the nature of Islamic beliefs and practices. The response of western ecclesiastical and secular authorities to renegades will also be considered. Further conversions of Christian peoples who had already for centuries been living under Muslim rule will not be examined, but only the adoption of Islam by those whose origins lay in western Christian countries or who were normally resident in these, and by westerners whose lands were newly conquered by Muslim powers after the eleventh century; and the focus will be mainly, though not exclusively, on the crusader states and the Iberian peninsula.

This study identifies the long lasting impacts of former cultivation on soils, seed banks and above-ground vegetation of limestone grasslands. We compared the resilience of three crop fields cultivated in the 19th century and abandoned (Abandoned Fields) with three grasslands which have never been cultivated (Old Grasslands). Grasslands were located in the Nature reserve of Grand-Pierre and Vitain valleys in France. Sites were identified using historical sources. Chemical and physical soil properties, above-ground vegetation and soil seed bank (0–10 cm and 10–20 cm) were studied. Data were analysed using a multivariate and univariate analyses to detect the effects/impacts of ancient cultivation. Our results clearly show that soil properties (e.g., calcium, carbonate, clay contents), above-ground vegetation (species diversity, moss and lichen cover) and seed bank (floristic composition, species-richness and diversity) are still impacted more than one century after their abandonment. Species richness of both above ground vegetation and seed bank are higher in old grasslands than in formerly cultivated fields. In the seed bank of the formerly cultivated soils we also found the presence of a very rare arable weed species (Althaea hirsuta) which has not been inventoried for a long time in the above-ground vegetation of the nature reserve. The resilience of formerly cultivated limestone grasslands might be influenced by the present management regime (site effect). Nevertheless, the resilience period of limestone grasslands is very long-more than one century-and return to an initial state might be difficult or impossible to reach.

This study identifies the long lasting impacts of former cultivation on soils, seed banks and above-ground vegetation of limestone grasslands. We compared the resilience of three crop fields cultivated in the 19th century and abandoned (Abandoned Fields) with three grasslands which have never been cultivated (Old Grasslands). Grasslands were located in the Nature reserve of Grand-Pierre and Vitain valleys in France. Sites were identified using historical sources. Chemical and physical soil properties, above-ground vegetation and soil seed bank (0-10 cm and 10-20 cm) were studied. Data were analysed using a multivariate and univariate analyses to detect the effects/impacts of ancient cultivation. Our results clearly show that soil properties (e.g., calcium, carbonate, clay contents), above-ground vegetation (species diversity, moss and lichen cover) and seed bank (floristic composition, species-richness and diversity) are still impacted more than one century after their abandonment. Species richness of both above ground vegetation and seed bank are higher in old grasslands than in formerly cultivated fields. In the seed bank of the formerly cultivated soils we also found the presence of a very rare arable weed species (Althaea hirsuta)which has not been inventoried for a long time in the above-ground vegetation of the nature reserve. The resilience of formerly cultivated limestone grasslands might be influenced by the present management regime (site effect). Nevertheless, the resilience period of limestone grasslands is very long-more than one century-and return to an initial state might be difficult or impossible to reach.

Cet article examine le devenir des frères du Temple après la dissolution de leur ordre en 1312, excepté en Angleterre et en Aragon (dont le cas a été étudié ailleurs). Il s’attache à établir dans quelle mesure furent appliqués les décrets de Clément V concernant les punitions, l’entretien des frères survivants et la résidence des frères absous, soit dans une maison ayant appartenu à l’ordre du Temple soit dans la maison d’un autre ordre religieux. Les décrets ultérieurs de Jean XXII qui enjoignaient aux Templiers d’intégrer d’autres ordres religieux comme membres ou au moins de les rejoindre temporairement et qui prescrivaient une réduction de leurs pensions sont aussi pris en compte. La documentation conservée est inégale mais indiscutablement le mode de vie des Templiers après 1312 a été très divers. Les Hospitaliers, rendus responsables du paiement des pensions après qu’ils eurent acquis les propriétés des Templiers, étaient soucieux de faire respecter les décisions pontificales, mais on constate ailleurs une attitude plus clémente et plus généreuse parfois, si bien que les Templiers, dont les rangs furent rapidement décimés par la mort, ont souvent pu vivre leurs derniers jours comme ils le souhaitaient.

Recognition of the strength of nonhuman primate models in investigating metabolic disorders has resulted in an expanded need for in vivo research techniques. We studied adipose metabolism in 10 baboons (13.0 ± 4.2 years old, 29.5 ± 5.5 kg). Part 1 evaluated the effect of different sedatives on the rate of appearance of plasma free fatty acids (RaFFA), assessed using 13C4-labeled palmitate infusion (7 µmol/kg/min). Animals, were studied with no sedation, with complete isoflurane sedation, and with minimal midazolam infusion (0.04 mg/kg/h), with the last scheme allowing for the most consistent values and animals that were visually more calm. In Part 2, RaFFA and RaGlycerol (D5-glycerol, 5 mg/kg lean body mass/h) were measured. From midnight to 0300, flux fell and came to a steady state between 0500 and 0700 h (RaFFA, 39.4 ± 29.8 µmol/kg fat mass/min; and RaGlycerol, 26.9 ± 7.3 µmol/kg/min). The RaFFA-to-RaGlycerol ratio was 1.5 ± 0.8 (49% reesterification). The decline in turnover throughout the night reflects natural circadian processes and was mirrored by reductions in FFA and glycerol to 0.62 and ± 0.14 and 0.16 and ± 0.03 mmol/l, respectively. The concurrent changes in both FFA and glycerol kinetics indicate physiologic validity of the method. These techniques will support needed research to determine mechanisms by which treatments act upon the adipocyte in vivo.

Recognition of the strength of nonhuman primate models in investigating metabolic disorders has resulted in an expanded need for in vivo research techniques. We studied adipose metabolism in 10 baboons (13.0 ± 4.2 years old, 29.5 ± 5.5 kg). Part 1 evaluated the effect of different sedatives on the rate of appearance of plasma free fatty acids (RaFFA), assessed using 13C4-labeled palmitate infusion (7 µmol/kg/min). Animals, were studied with no sedation, with complete isoflurane sedation, and with minimal midazolam infusion (0.04 mg/kg/h), with the last scheme allowing for the most consistent values and animals that were visually more calm. In Part 2, RaFFA and RaGlycerol (D5-glycerol, 5 mg/kg lean body mass/h) were measured. From midnight to 0300, flux fell and came to a steady state between 0500 and 0700 h (RaFFA, 39.4 ± 29.8 μmol/kg fat mass/min; and RaGlycerol, 26.9 ± 7.3 μmol/kg/min). The RaFFA-to-RaGlycerol ratio was 1.5 ± 0.8 (49% reesterification). The decline in turnover throughout the night reflects natural circadian processes and was mirrored by reductions in FFA and glycerol to 0.62 and ± 0.14 and 0.16 and ± 0.03 mmol/l, respectively. The concurrent changes in both FFA and glycerol kinetics indicate physiologic validity of the method. These techniques will support needed research to determine mechanisms by which treatments act upon the adipocyte in vivo.

ABSTRACTSequence-based typing (SBT) is a powerful method based on the sequencing of seven genes of Legionella pneumophilaisolates. SBT performed directly on clinical samples has been used only in a limited number of cases. In our study, its efficiency was tested with 63 legionellosis respiratory samples. Sixty-three clinical samples, which included 23 samples from sporadic cases and 40 collected during four French outbreaks, confirmed by culture or urinary antigen testing and all positive by L. pneumophilaquantitative PCR were subtyped by SBT according to the European Working Group for LegionellaInfections standard scheme. Only 28.6% of the samples provided nucleotide sequences by SBT. Nested-PCR-based SBT (NPSBT) applied to the same respiratory samples was thus evaluated with new PCR primers surrounding the first set of primers used for the SBT. Sequencing results were obtained with 90.5% of the samples. Complete allelic profiles (seven genes sequenced) were obtained for 3.2% versus 53.9% of the samples by SBT and NPSBT, respectively. More importantly, of the 28 culture-negative samples, only 4 did not give any sequencing results. Taken together, NPSBT applied directly to clinical specimens significantly improved epidemiological typing compared to the initial SBT, in particular when no isolates are available.

Simulations of the land surface carbon cycle typically compress functional diversity into a small set of plant functional types (PFT), with parameters defined by the average value of measurements of functional traits. In most earth system models, all wild plant life is represented by between five and 14 PFTs and a typical grid cell (≈100 × 100 km) may contain a single PFT. Model logic applied to this coarse representation of ecological functional diversity provides a reasonable proxy for the carbon cycle, but does not capture the non‐linear influence of functional traits on productivity. Here we show through simulations using the Energy Exascale Land Surface Model in 15 diverse terrestrial landscapes, that better accounting for functional diversity markedly alters predicted total carbon uptake. The shift in carbon uptake is as great as 30% and 10% in boreal and tropical regions, respectively, when compared to a single PFT parameterized with the trait means. The traits that best predict gross primary production vary based on vegetation phenology, which broadly determines where traits fall within the global distribution. Carbon uptake is more closely associated with specific leaf area for evergreen PFTs and the leaf carbon to nitrogen ratio in deciduous PFTs. Plants play a critical role in the global carbon cycle, and diversity has been shown to influence vegetation productivity. However, when the land surface is simulated in a global model all wild plant life is reduced to a small number of plant functional types. Here we estimate how incorporating diversity influences ecosystem carbon uptake in 15 globe spanning landscapes. We find that diversity has a strong influence on modeled productivity, particularly in the arctic and tropics. Further, we find that whether plants shed their leaves annually has a strong influence on where traits fall within the global distribution and thus how traits and productivity interact. We implemented distributions of leaf economic spectrum traits in a land surface model in 15 diverse landscapesTrait variation has a substantial influence on gross primary production (GPP)Phenology plays a key role in guiding where traits fall within the global trait distribution and hence trait‐GPP relationships We implemented distributions of leaf economic spectrum traits in a land surface model in 15 diverse landscapes Trait variation has a substantial influence on gross primary production (GPP) Phenology plays a key role in guiding where traits fall within the global trait distribution and hence trait‐GPP relationships

Observed rises in taxic diversity could reflect bias of the fossil record or a genuine diversification. Here we outline a new method that attempts to differentiate between these two possible explanations. The method is based on the calculations of average ghost lineage duration through successive intervals of time. Biases due to variation in preservational conditions affect taxa independently from their position in the tree of life. A genuine radiation event will affect some parts of the tree of life more than others. During periods of rapid diversification, there will be a high proportion of new taxa showing short ghost lineages and therefore the average ghost lineage duration will drop as diversity rises, allowing us to distinguish such events from preservational bias during which ghost lineage duration remains unchanged. We test the method on Aptian–Maastrichtian (Cretaceous) ray-finned fish diversity. The result shows that a peak of diversity in the Cenomanian is associated with a drop in average ghost lineage duration, indicating that a genuine biological radiation occurred at that time.

The Upper Cretaceous fish †Tomognathus mordax Dixon, 1850, is redescribed, based on newly acid-prepared material that reveals many new structures and reinterpretations of some parts of anatomy previously described. The cranium shows the absence of a supraoccipital, a double jaw joint involving a symplectic and quadrate, a lower jaw incorporating a coronoid, prearticular and a surangular, concave shape of the posterior margin of the maxilla, a single supramaxiila, a ‘V’-shaped median rostral with lateral horns and an interopercle that lies in series with the subopercle. These features suggest affinities with the Halecomorphi. Within Halecomorphi, character conflict means that †Tomognathus may only be placed as Superfamily Amioidea incertae sedis. It is highly apomorphic in showing parietals, frontals, premaxillae and vomers all fused into median elements, a parasphenoid with scythe-like processes developed along the ascending wings and an infraorbital series reduced to tube-like elements. †Tomognathus is one of only three halecomorphs recorded from the English Chalk.

ABSTRACTMethicillin-resistant Staphylococcus aureus(MRSA) clones harboring the toxic shock syndrome toxin 1 (tst) gene have been detected in France and in Switzerland since 2002. During a passive survey conducted between 2002 and 2003, we collected 103 tst-positive S. aureusisolates from 42 towns in France, of which 27 were resistant to methicillin. The tst-positive MRSA belonged to two clones: a major clone comprising 25 isolates of sequence type (ST) 5 and agrgroup 2 and a minor clone comprising two isolates of ST30 and agr3. The tst-positive MRSA clones were associated with both hospital-acquired (12 cases) and community-acquired (8 cases) infections. The MRSA clones were mainly isolated from children (overall median age, 3 years). They caused a variety of clinical syndromes, including toxic shock syndrome and suppurative infections. Both clones were found to harbor a type IV staphylococcal chromosomal cassette mec(SCCmec) and to have similar antibiotic resistance profiles (usually resistant to oxacillin, kanamycin, and tobramycin and with intermediate resistance to fusidic acid). The origin of these clones is unclear. The tst-positive agr2MRSA clone has the same sequence type (ST5) of two pandemic nosocomial MRSA clones, namely, the Pediatric clone and the New York/Japan clone. These findings suggest that all these clones are phylogenetically related. The pulsotype of the tst-positive MRSA clones differed from that of methicillin-sensitive S. aureus(MSSA) clones by a single band involving the SCCmecelement. These findings suggest that the tst-positive MRSA clones may have emerged from their respective MSSA counterparts.

Methicillin-resistant Staphylococcus aureus (MRSA) clones harboring the toxic shock syndrome toxin 1 (tst) gene have been detected in France and in Switzerland since 2002. During a passive survey conducted between 2002 and 2003, we collected 103 tst-positive S. aureus isolates from 42 towns in France, of which 27 were resistant to methicillin. The tst-positive MRSA belonged to two clones: a major clone comprising 25 isolates of sequence type (ST) 5 and agr group 2 and a minor clone comprising two isolates of ST30 and agr3. The tst-positive MRSA clones were associated with both hospital-acquired (12 cases) and community-acquired (8 cases) infections. The MRSA clones were mainly isolated from children (overall median age, 3 years). They caused a variety of clinical syndromes, including toxic shock syndrome and suppurative infections. Both clones were found to harbor a type IV staphylococcal chromosomal cassette mec (SCCmec) and to have similar antibiotic resistance profiles (usually resistant to oxacillin, kanamycin, and tobramycin and with intermediate resistance to fusidic acid). The origin of these clones is unclear. The tst-positive agr2 MRSA clone has the same sequence type (ST5) of two pandemic nosocomial MRSA clones, namely, the Pediatric clone and the New York/Japan clone. These findings suggest that all these clones are phylogenetically related. The pulsotype of the tst-positive MRSA clones differed from that of methicillin-sensitive S. aureus (MSSA) clones by a single band involving the SCCmec element. These findings suggest that the tst-positive MRSA clones may have emerged from their respective MSSA counterparts.

SynopsisThe Upper Cretaceous fish †Tomognathus mordaxDixon, 1850, is redescribed, based on newly acid‐prepared material that reveals many new structures and reinterpretations of some parts of anatomy previously described. The cranium shows the absence of a supraoccipital, a double jaw joint involving a symplectic and quadrate, a lower jaw incorporating a coronoid, prearticular and a surangular, concave shape of the posterior margin of the maxilla, a single supramaxiila, a ‘V'‐shaped median rostral with lateral horns and an interopercle that lies in series with the subopercle. These features suggest affinities with the Halecomorphi. Within Halecomorphi, character conflict means that †Tomognathusmay only be placed as Superfamily Amioidea incertae sedis.It is highly apomorphic in showing parietals, frontals, premaxillae and vomers all fused into median elements, a parasphenoid with scythe‐like processes developed along the ascending wings and an infraorbital series reduced to tube‐like elements. †Tomognathusis one of only three halecomorphs recorded from the English Chalk.

X-linked lymphoproliferative disease (XLP) is characterized by abnormal immune responses to Epstein-Barr virus attributed to inactivating mutations of the SAP gene. Previous studies showed immunoglobulin E (IgE) deficiency and low serum IgG levels in Sap-deficient mice before and after viral infections, which are associated with impaired CD4+ T-helper function. In the present work, we find that signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is expressed in B cells and this expression is down-regulated after stimulation with lipopolysaccharide (LPS) and interleukin 4 (IL-4). We demonstrate that B cells from Sap-deficient mice exhibit reduced IgG and IgA production in vitro. This impairment correlates with decreased circular transcript levels of Iα, Iγ2a, Iγ2b, and Iγ3 after stimulation, which indicate a defective Ig switch recombination in Sap-deficient B cells. While XLP is believed to cause defects in T, natural killer T (NKT), and natural killer (NK) cells, our results indicate that B cells are also affected. (Blood. 2005;106:2069-2075)

X-linked lymphoproliferative disease (XLP) is characterized by abnormal immune responses to Epstein-Barr virus attributed to inactivating mutations of the SAPgene. Previous studies showed immunoglobulin E (IgE) deficiency and low serum IgG levels in Sap-deficient mice before and after viral infections, which are associated with impaired CD4+T-helper function. In the present work, we find that signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is expressed in B cells and this expression is down-regulated after stimulation with lipopolysaccharide (LPS) and interleukin 4 (IL-4). We demonstrate that B cells from Sap-deficient mice exhibit reduced IgG and IgA production in vitro. This impairment correlates with decreased circular transcript levels of Iα, Iγ2a, Iγ2b, and Iγ3 after stimulation, which indicate a defective Ig switch recombination in Sap-deficient B cells. While XLP is believed to cause defects in T, natural killer T (NKT), and natural killer (NK) cells, our results indicate that B cells are also affected. (Blood. 2005;106:2069-2075)

The taking of vows in a military order, as in other religious foundations, created a lifelong obligation. The phrase stabilitas loci, which is encountered in some documents relating to these orders, did not imply an undertaking to stay permanently in the same convent, but signified that those who had made their profession should remain in the same order for life. This requirement found expression especially in papal decrees, although orders' regulations give information about the punishment of apostates. As in other religious establishments, a transfer to another order provided the sole permitted exception, but this was allowed only under certain conditions.

Many compendia at the species, genus and family levels document the fossil record, but these are not standardized, nor usually critical in content, and few are available on the World Wide Web. The sampling of the available record is good for organisms with fossilizable parts, but preservational constraints on the entire morphology, life history and geographical distribution lead to difficulties in recognizing and naming species. We recommend abandoning some of the palaeontological species concepts such as chronospecies and stratospecies, and we advocate species recognition based on unique combinations of characters. The compilation of species lists is extremely time consuming, and given the inherent problems we suggest that compilation of generic lists is a more achievable goal because genera are recognized by definitive morphological characters. In calculating taxon duration, care must be taken to distinguish between mono–, para– and polyphyletic groups, the first being the only reliable unit for use in calculating diversity curves. We support the inclusion of fossils into classifications based on Recent organisms, but we recognize some of the problems this may pose for standard Linnaean classifications. Web–based taxonomy is the way forward, having the advantages of speed and currency of information dissemination, universal access with links to primary literature and increasingly sophisticated imagery. These advantages over conventional outlets will only be realized with careful Web design and a commitment to maintenance.

A new fish fauna is described from the middle Cenomanian of Namoura, Lebanon. Thirty species are described of which 13 are new. Six new genera are erected to contain seven of these new species. These new taxa include the teleosts Ctenodentelops striatus gen. et sp. nov. (Elopidae), Lebonichthys namourensis sp. nov. (Albulidae), Triplomystus noorae gen. et sp. nov. and Triplomystus oligoscutatus gen. et sp. nov. (Paraclupeidae), Armigatus namourensis sp. nov. and Armigatus alticorpus sp. nov. (Clupeomorpha incertae sedis), Scombroclupea diminuta sp. nov. (Clupeiformes incertae sedis), Enchodus mecoanalis sp. nov. (Enchodontidae), Serrilepis prymnostrigos gen. et sp. nov. and Serrilepis minor gen. et sp. nov. (Halecidae), Paracentrus lebanonensis gen. et sp. nov. (Holocentroidea) and Gigapteryx lebanonensis gen. et sp. nov. (Euacanthopterygii incertae sedis). Two new species of the aspidorhynchid genus Belonostomus are recognised but left un-named awaiting better material, as is one new species of pycnodont. Comparison of taxic composition of the faunas at Hakel, Hajula and Namoura suggests that at both species and generic level there is considerably more similarity between Hakel and Hajula than between either and Namoura. Furthermore, counts of actual specimens belonging to individual clades reveals a poverty of aulopiforms and myctophiforms at Namoura and may add to the evidence from non-fish taxa that Namoura was much nearer to the contemporaneous land than was either Hakel or Hajula and may be of a slightly different age. Wider comparisons with other Cenomanian localities surrounding central Tethys suggest a phenetically closer relationship between Morocco, Lebanon and Slovenia than between any of these localities and Southeast England.

SynopsisA new fish fauna is described from the middle Cenomanian of Namoura, Lebanon. Thirty species are described of which 13 are new. Six new genera are erected to contain seven of these new species. These new taxa include the teleosts Ctenodentelops striatusgen. et sp. nov. (Elopidae), Lebonichthys namourensissp. nov. (Albulidae), Triplomystus nooraegen. et sp. nov. and Triplomys‐tus oligoscutatusgen. et sp. nov. (Paraclupeidae), Armigatus namourensissp. nov. and Armigatus alticorpussp. nov. (Clupeomorpha incertae sedis), Scombroclupea diminutasp. nov. (Clupeiformes incertae sedis), Enchodus mecoanalissp. nov. (Enchodontidae), Serrilepis prymnostrigosgen. et sp. nov. and Serrilepis minorgen. et sp. nov. (Halecidae), Paracentrus lebanonensisgen. et sp. nov. (Holocentroidea) and Gigapteryx lebanonensisgen. et sp. nov. (Euacanthopterygii incertae sedis).Two new species of the aspidorhynchid genus Belonostomusare recognised but left un‐named awaiting better material, as is one newspecies of pycnodont. Comparison of taxic composition of the faunas at Hakel, Hajula and Namoura suggests that at both species and generic level there is considerably more similarity between Hakel and Hajula than between either and Namoura. Furthermore, counts of actual specimens belonging to individual clades reveals a poverty of aulopiforms and myctophiforms at Namoura and may add to the evidence from non‐fish taxa that Namoura was much nearer to the contemporaneous land than was either Hakel or Hajula and may be of a slightly different age. Wider comparisons with other Cenomanian localities surrounding central Tethys suggest a phenetically closer relationship between Morocco, Lebanon and Slovenia than between any of these localities and Southeast England.

“The Charitable Activities of the Templars.” Testimonies from the Templar trial as well as twelfth- and thirteenth century sources are used to determine the extent to which the Templars engaged in almsgiving, hospitality, and the protecting of pilgrims. The Order was under an obligation to dispense alms and to ensure the safety of pilgrims, and clearly almsgiving was undertaken throughout the Order’s history in all provinces, although alms may have been reduced in some districts, particularly in the later thirteenth century, partly because of financial difficulties. The protecting of pilgrims appears, however, to have occurred only in the Holy Land, and even there this activity was restricted by Muslim conquests. It has often been claimed that the Templars also maintained hospitals, but the Order was under no obligation to provide accommodation for travelers or the sick, and it is to be doubted whether it did so. It seems to have devoted its inadequate resources to the activities which it was bound to undertake.

The expression of most Staphylococcus aureus virulence factors is controlled by the agr locus, which encodes a two-component signaling pathway whose activating ligand is an agr-encoded autoinducing peptide (AIP). A polymorphism in the amino acid sequence of the AIP and of its corresponding receptor divides S. aureus strains into four major groups. Within a given group, each strain produces a peptide that can activate the agr response in the other member strains, whereas the AIPs belonging to different groups are usually mutually inhibitory. We investigated a possible relationship between agr groups and human S. aureus disease by studying 198 S. aureus strains isolated from 14 asymptomatic carriers, 66 patients with suppurative infection, and 114 patients with acute toxemia. The agr group and the distribution of 24 toxin genes were analyzed by PCR, and the genetic background was determined by means of amplified fragment length polymorphism (AFLP) analysis. The isolates were relatively evenly distributed among the four agrgroups, with 61 strains belonging to agr group I, 49 belonging to group II, 43 belonging to group III, and 45 belonging to group IV. Principal coordinate analysis performed on the AFLP distance matrix divided the 198 strains into three main phylogenetic groups, AF1 corresponding to strains of agr group IV, AF2 corresponding to strains of agr groups I and II, and AF3 corresponding to strains of agr group III. This indicated that the agr type was linked to the genetic background. A relationship between genetic background, agr group, and disease type was observed for several toxin-mediated diseases: for instance, agr group IV strains were associated with generalized exfoliative syndromes, and phylogenetic group AF1 strains with bullous impetigo. Among the suppurative infections, endocarditis strains mainly belonged to phylogenetic group AF2 and agr groups I and II. While these results do not show a direct role of the agr type in the type of human disease caused by S. aureus, the agr group may reflect an ancient evolutionary division of S. aureus in terms of this species' fundamental biology.

ABSTRACTThe expression of most Staphylococcus aureusvirulence factors is controlled by the agrlocus, which encodes a two-component signaling pathway whose activating ligand is an agr-encoded autoinducing peptide (AIP). A polymorphism in the amino acid sequence of the AIP and of its corresponding receptor divides S. aureusstrains into four major groups. Within a given group, each strain produces a peptide that can activate the agrresponse in the other member strains, whereas the AIPs belonging to different groups are usually mutually inhibitory. We investigated a possible relationship between agrgroups and human S. aureusdisease by studying 198 S. aureusstrains isolated from 14 asymptomatic carriers, 66 patients with suppurative infection, and 114 patients with acute toxemia. The agrgroup and the distribution of 24 toxin genes were analyzed by PCR, and the genetic background was determined by means of amplified fragment length polymorphism (AFLP) analysis. The isolates were relatively evenly distributed among the four agrgroups, with 61 strains belonging to agrgroup I, 49 belonging to group II, 43 belonging to group III, and 45 belonging to group IV. Principal coordinate analysis performed on the AFLP distance matrix divided the 198 strains into three main phylogenetic groups, AF1 corresponding to strains of agrgroup IV, AF2 corresponding to strains of agrgroups I and II, and AF3 corresponding to strains of agrgroup III. This indicated that the agrtype was linked to the genetic background. A relationship between genetic background, agrgroup, and disease type was observed for several toxin-mediated diseases: for instance, agrgroup IV strains were associated with generalized exfoliative syndromes, and phylogenetic group AF1 strains with bullous impetigo. Among the suppurative infections, endocarditis strains mainly belonged to phylogenetic group AF2 and agrgroups I and II. While these results do not show a direct role of the agrtype in the type of human disease caused by S. aureus, the agrgroup may reflect an ancient evolutionary division of S. aureusin terms of this species’ fundamental biology.

The PhyloCodesuggests that by adopting its rules, taxonomists will gain clarity, uniqueness and stability compared with the use of Linnaean Taxonomy. This claim is questioned here by suggesting (1) that replacing the Types of Linnaean Taxonomy with the Specifiers of PhyloCodeincreases the complexity of decisions which have to be made, some of which go beyond nomenclature; (2) deciding which PhyloCodedefinition of a name to use demands knowledge of phylogenetic support and likelihood of future changes in ideas of relationships; (3) Phylogenetic Nomenclature will have limited value because it names only monophyletic groups, and (4) confusion over naming taxa is not avoided by the PhyloCodeand can lead to problems when used alongside Linnaean Taxonomy. The problems concerning Linnaean rank and raised by Phylogenetic Nomenclature are upheld.

The anatomy of the osteoglossomorph Palaeonotopterus greenwoodiForey is redescribed on the basis of more complete material than used in the original description. This new material shows large rounded and attached parasphenoid tooth plates with a Plethodus-like histology. We are therefore able to associate some species ofPlethoduswith a skull. Not all species of Plethodusmay belong to the same kind of fish: specifically,Plethodus oblongusDixon, which is known from articulated skull material, appears to be a very different kind of fish.Palaeonotopterusshows a mixture of notopterid and mormyroid characters. With notopterids Palaeonotopterusshares an elongate foramen for V+VII straddling the suture between prootic and pterosphenoid in the orbital wall, an auditory fenestra between the prootic and basioccipital (homoplastic with Hiodon), a sagitta with a prominent anterior process (inferred in Palaeonotopterusfrom the shape of the labyrinth cavity). With primitive mormyroids Palaeonotopterusshares a similar and distinctively shaped supraoccipital crest and a suture between the paraÍsphenoid and autosphenotic. A supraorbital branch of the otic sensory canal, formerly thought to be a character of notopterids, is present in mormyroids and therefore is interpreted as a character of notopterids+mormyroids.

Two cases of legionellosis occurring 3 years apart were acquired in the same French thermal spa and were apparently due to the same strain of Legionella pneumophila serogroup 1, as shown by genomic macrorestriction analysis. Minor differences between the two isolates were found by random amplification PCR profiling which showed an additional band with one of the isolates. Analysis of 107 L. pneumophila strains isolated from the spa waters by genome macrorestriction failed to identify the infective strain, but a closely related L. pneumophila serogroup 3 strain differing from the clinical isolates by only one band was found. To determine if the clinical L. pneumophila serogroup 1 isolates was better adapted for intracellular multiplication than related serogroup 3 environmental isolates, the growth kinetics of six isolates were determined in co-culture with Acanthamoeba lenticulata. One clinical isolate failed to grow within amoeba, while the other clinical isolate yielded the highest increase in bacterial cell count per amoeba (1200 %) and the environmental isolates gave intermediate values. Genetic analysis of L. pneumophila isolates by DNA macrorestriction does not therefore appear to reflect their growth kinetics within amoeba, and is not sufficiently discriminatory to identify potentially virulent strains.