Biometry of Cenomanian–Turonian placoliths: a proxy for changes of fertility and surface‐water temperature?

Most publications discussing Cenomanian–Turonian calcareous nannofossils focus on abundance fluctuations across the boundary interval. So far, there have been no studies that deal with the influence of palaeoenvironmental changes on the size of common Cenomanian–Turonian nannofossil taxa. The genera Biscutum, Broinsonia, Prediscosphaera, Retecapsa and Watznaueria have therefore been analysed from 19 samples of Cenomanian–Turonian age from the Goban Spur, northeast Atlantic. The genus Biscutum shows a slight decrease of mean length from 4.14 μm in the Cenomanian to 3.94 μm in the Turonian. Broinsonia is marked by a decrease from 6.07 μm in the Cenomanian to 5.64 μm in the Turonian. On the other hand, Prediscospheara increases in size from 4.98 μm in the Cenomanian to 5.61 μm in the Turonian. Two genera (Retecapsa, Watznaueria) show no significant changes in their mean length. The mean size of Biscutum is perhaps controlled by nutrients, where larger specimens may have preferred the more fertile palaeoenvironment of the Late Cenomanian. The size decrease of Biscutum in the Turonian is probably related to reduced nutrient availability. The genus Prediscosphaera spp., may have favoured low‐fertility conditions, as its mean size increases in the Turonian. A worldwide decline of the frequency of Broinsonia spp. during the Cenomanian–Turonian transition implies that this genus is not solely controlled by the nutrient content. The size of Broinsonia spp. may have been therefore influenced by the latest Cenomanian warming event. The increase in sea‐surface temperature may have been unfavourable for Broinsonia spp. as reflected by decreasing mean size and frequency. □Calcareous nannofossils, biometry, morphometry, Oceanic Anoxic Event 2.     

Phylogenetic analysis reveals that Rhabdopleura is an extant graptolite

A phylogenetic analysis of morphological data from modern pterobranch hemichordates (Cephalodiscus, Rhabdopleura) and representatives of each of the major graptolite orders reveals that Rhabdopleura nests among the benthic, encrusting graptolite taxa as it shares all of the synapomorphies that unite the graptolites. Therefore, rhabdopleurids can be regarded as extant members of the Subclass Graptolithina (Class Pterobranchia). Combined with the results of previous molecular phylogenetic studies of extant deuterostomes, these results also suggest that the Graptolithina is a sister taxon to the Subclass Cephalodiscida. The Graptolithina, as an important component of Early–Middle Palaeozoic biotas, provide data critical to our understanding of early deuterostome phylogeny. This result allows one to infer the zooid morphology, mechanics of colony growth and palaeobiology of fossil graptolites in direct relation to the living members of the clade. The Subdivision Graptoloida (nom. transl.), which are all planktic graptolites, is well supported in this analysis. In addition, we recognize the clade Eugraptolithina (nov.). This clade comprises the Graptoloida and all of the other common and well‐known graptolites of the distinctive Palaeozoic fauna. Most of the graptolites traditionally regarded as tuboids and dendroids appear to be paraphyletic groups within the Eugraptolithina; however, Epigraptus is probably not a member of this clade. The Eugraptolithina appear to be derived from an encrusting, Rhabdopleura‐like species, but the available information is insufficient to resolve the phylogeny of basal graptolites. The phylogenetic position of Mastigograptus and the status of the Dithecoidea and Mastigograptida also remain unresolved. □ Biodiversity, Cambrian, Hemichordata, Deuterostomia, Ordovician.     

The Challenge of Antibiotic-Resistant Staphylococcus: Lessons from Hospital Nurseries in the mid-20th Century

In the late 1940s, epidemics of antibiotic-resistant strains of Staphylococcus aureus began to plague postpartum nurseries in hospitals across the United States. Exacerbated by overcrowding and nursing shortages, resistant S. aureus outbreaks posed a novel challenge to physicians and nurses heavily reliant on antibiotics as both prophylaxis and treatment. This paper explores the investigation of the reservoir, mode of transmission, and virulence of S. aureus during major hospital outbreaks and the subsequent implementation of novel infection control measures from the late 1940s through the early 1960s. The exploration of these measures reveals a shift in infection control policy as hospitals, faced with the failure of antibiotics to slow S. aureus outbreaks, implemented laboratory culture routines, modified nursery structure and layout, and altered nursing staff procedures to counter various forms of S. aureus transmission. Showcasing the need for widespread epidemiologic surveillance, ultimately manifesting itself in specialized “hospital epidemiology” training promoted in the 1970s, the challenges faced by hospital nurses in the 1950s prove highly relevant to the continued struggle with methicillin-resistant Staphylococcus aureus (MRSA) and other resistant nosocomial infections.     

Discovery and SAR of PF-4693627, a potent,selective and orally bioavailable mPGES-1 inhibitor for the potential treatment of inflammation

Inhibition of mPGES-1, the terminal enzyme in the arachidonic acid/COX pathway to regulate the production of pro-inflammatory prostaglandin PGE2, is considered an attractive new therapeutic target for safe and effective anti-inflammatory drugs. The discovery of a novel series of orally active, selective benzoxazole piperidinecarboxamides as mPGES-1 inhibitors is described. Structure–activity optimization of lead 5 with cyclohexyl carbinols resulted in compound 12, which showed excellent in vitro potency and selectivity against COX-2, and reasonable pharmacokinetic properties. Further SAR studies of the benzoxazole ring substituents lead to a novel series of highly potent compounds with improved PK profile, including 23, 26, and 29, which were effective in a carrageenan-stimulated guinea pig air pouch model of inflammation. Based on its excellent in vitro and in vivo pharmacological, pharmacokinetic and safety profile and ease of synthesis, compound 26 (PF-4693627) was advanced to clinical studies.     

Somatoform disorders among patients attending walk-in clinics in Trinidad: prevalence and association with depression and anxiety

Objectives Somatoform disorders are common in international primary care settings, but have been little studied in the developing world. The objective of this study was to determine the prevalence of severe undifferentiated somatoform disorder, and its relationship to depression and anxiety, among patients attending walk-in clinics in Trinidad.Methods The study participants, who were all aged 18 years or older and attending walk-in clinics at 16 randomly selected health centres, were surveyed between May and August 2007 using the PRIME-MD questionnaire.Results There were 594 participants (the response rate was 92%), of whom 72.7% were female. Their ages ranged from 18 to 93 years, and 54.5% were over 50 years of age. In total, 37.2% were married and 25.9% were single. Indo-Trinidadians represented 43.1% and Afro-Trinidadians represented 36% of the study sample; 56.5% of the participants reported that their income was less than US$ 400 per month, and 65.7% were unemployed. At walk-in clinics in Trinidad, the estimated prevalence of severe undifferentiated somatoform disorder was 10.3% (95% CI: 7.86–12.74), that of hypochondriasis was 28.5% (95% CI: 24.9–32.1), and that of body dysmorphic disorder was 15.8% (95% CI: 11.9–18.7). Severe undifferentiated somatoform disorder was statistically significantly associated with gender and ethnicity but not with age, level of education, employment status or income. Chi-square testing found significant associations between the presence of severe undifferentiated somatoform disorder and both depression and anxiety (P < 0.05), between hypochondriasis and both anxiety and depression (P < 0.05), and between body dysmorphic disorder and depression (P < 0.05) but not anxiety. Regression analysis suggested that the demographic features that predicted severe undifferentiated somatoform disorder were being female or Indo-Trinidadian.Conclusions Walk-in clinics in Trinidad that serve older patients on a lower income have a high proportion of patients with somatoform disorders as measured by the PRIME-MD scale. These patients exhibit many features of anxiety and depression. These findings have implications for medical training and service delivery.     

the JigCell model builder and run manager

SUMMARY: We describe the JigCell Model Builder (JCMB), a tool for creating biochemical reaction network models. JCMB is designed for ease of use and its interface uses the standard spreadsheet metaphor. The JigCell Run Manager (JCRM) is a tool for organizing the large collections of simulation runs typically required by reaction network modeling activities. AVAILABILITY: JCMB and JCRM are part of the JigCell suite available at http://jigcell.biol.vt.edu.     

Turtle phylogeny: insights from a novel nuclear intron

Introns have gained considerable popularity as markers for molecular phylogenetics. However, no primers exist for a nuclear intron that amplifies across all turtles. Available data from morphology and mitochondrial DNA have not unambiguously resolved relationships within the superfamily Trionychoidea and the family Chelidae, which together form a large portion of extant turtle diversity. We tested the phylogenetic utility of a novel intron from the RNA fingerprint protein 35 (R35) as applied to these two areas of turtle systematics. We found the intron to be a single-copy locus that provides excellent resolving power for lineages among turtles, though problems with alignment made it impossible to infer deeper amniote relationships. Maximum parsimony and maximum likelihood both demonstrated the polyphyly of Trionychoidea and the reciprocal monophyly of Australian/New Guinea and South American chelid turtles. This is the first study to resolve such relationships with strong statistical support, and we suggest that R35 holds great promise for resolving additional persistent problems in the phylogeny of living turtles.     

Phylogenetic hypotheses for the turtle family Geoemydidae

The turtle family Geoemydidae represents the largest, most diverse, and most poorly understood family of turtles. Little is known about this group, including intrafamilial systematics. The only complete phylogenetic hypothesis for this family positions geoemydids as paraphyletic with respect to tortoises, but this arrangement has not been accepted by many workers. We compiled a 79-taxon mitochondrial and nuclear DNA data set to reconstruct phylogenetic relationships for 65 species and subspecies representing all 23 genera of the Geoemydidae. Maximum parsimony (MP) and maximum-likelihood (ML) analyses and Bayesian analysis produced similar, well-resolved trees. Our analyses identified three main clades comprising the tortoises (Testudinidae), the old-world Geoemydidae, and the South American geoemydid genus Rhinoclemmys. Within Geoemydidae, many nodes were strongly supported, particularly based on Bayesian posterior probabilities of the combined three-gene dataset. We found that adding data for a subset of taxa improved resolution of some deeper nodes in the tree. Several strongly supported groupings within the Geoemydidae demonstrate non-monophyly of some genera and possible interspecific hybrids, and we recommend several taxonomic revisions based on available evidence.     

The MHC class I-like IgG receptor controls perinatal IgG transport,IgG homeostasis,and fate of IgG-Fc-coupled drugs

Abs of the IgG isotype are efficiently transported from mother to neonate and have an extended serum t(1/2) compared with Abs of other isotypes. Circumstantial evidence suggests that the MHC class I-related protein, the neonatal FcR (FcRn), is the FcR responsible for both in vivo functions. To understand the phenotypes imposed by FcRn, we produced and analyzed mice with a defective FcRn gene. The results provide direct evidence that perinatal IgG transport and protection of IgG from catabolism are mediated by FcRn, and that the latter function is key to IgG homeostasis, essential for generating a potent IgG response to foreign Ags, and the basis of enhanced efficacy of Fc-IgG-based therapeutics. FcRn is therefore a promising therapeutic target for enhancing protective humoral immunity, treating autoimmune disease, and improving drug efficacy.     

Physical map of 1p36, placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome

Monosomy 1p36 is the most common terminal deletion syndrome. This contiguous gene deletion syndrome is presumably caused by haploinsufficiency of a number of genes. We have constructed a contig of overlapping large-insert clones for the most distal 10.5 Mb of 1p36, evaluated the deletion sizes in 61 subjects with monosomy 1p36 from 60 families, and created a natural deletion panel. We found pure terminal deletions, interstitial deletions, derivative chromosomes, and more complex rearrangements. Breakpoints were "binned" into 0.5-Mb regions. Analyses revealed some clustering of breakpoints but no single common breakpoint. Determination of the parental origin showed that 60% of de novo 1p36 terminal deletions arose from the maternally inherited chromosome. Of the 61 subjects, 30 were examined systematically through a protocol at the Texas Children's Hospital General Clinical Research Center. Specifically, we report hearing evaluations, palatal and ophthalmological examinations, echocardiograms, neurological assessments, and thyroid function tests. To our knowledge, this systematic molecular and clinical characterization of monosomy 1p36 is the largest and most comprehensive study of this deletion syndrome to date. Many cytogenetically visible, apparent terminal deletions are more complex than anticipated by cytogenetics, as revealed at the molecular level by our study. Our clinical findings allow for the more accurate recognition of the syndrome and for proper medical evaluation.