Gene duplication is infrequent in the recent evolutionary history of RNA viruses.
Gene duplication generates genetic novelty and redundancy and is a major mechanism of evolutionary change in bacteria and eukaryotes. To date, however, gene duplication has been reported only rarely in RNA viruses. Using a conservative BLAST approach we systematically screened for the presence of duplicated (i.e., paralogous) proteins in all RNA viruses for which full genome sequences are publicly available. Strikingly, we found only nine significantly supported cases of gene duplication, two of which are newly described here--in the 25 and 26 kDa proteins of Beet necrotic yellow vein virus (genus Benyvirus) and in the U1 and U2 proteins of Wongabel virus (family Rhabdoviridae). Hence, gene duplication has occurred at a far lower frequency in the recent evolutionary history of RNA viruses than in other organisms. Although the rapidity of RNA virus evolution means that older gene duplication events will be difficult to detect through sequence-based analyses alone, it is likely that specific features of RNA virus biology, and particularly intrinsic constraints on genome size, reduce the likelihood of the fixation and maintenance of duplicated genes.


Reproductive success of Bornean orangutan males: scattered in time but clustered in space.
The social and mating systems of orangutans, one of our closest relatives, remain poorly understood. Orangutans (Pongo spp.) are highly sexually dimorphic and females are philopatric and maintain individual, but overlapping home ranges, whereas males disperse, are non-territorial and wide-ranging, and show bimaturism, with many years between reaching sexual maturity and attaining full secondary sexual characteristics (including cheek pads (flanges) and emitting long calls). We report on 21 assigned paternities, among 35 flanged and 15 unflanged, genotyped male Bornean orangutans (Pongo pygmaeus wurmbii), studied from 2003 to 2018 in Tuanan (Central Kalimantan, Indonesia). All 10 infants born since mid-2003 with an already identified sire were sired by flanged males. All adult males ranged well beyond the study area (c. 1000 ha), and their dominance relations fluctuated even within short periods. However, 5 of the 10 identified sires had multiple offspring within the monitored area. Several sired over a period of c. 10 years, which overlapped with siring periods of other males. The long-calling behavior of sires indicated they were not consistently dominant over other males in the area around the time of known conceptions. Instead, when they were seen in the area, the known sires spent most of their time within the home ranges of the females whose offspring they sired. Overall, successful sires were older and more often resident than others. It is difficult to assess reproductive success for individuals of long-lived species, especially for dispersing males, who cannot be monitored throughout their lives. Due to extremely long interbirth intervals, orangutans have highly male-skewed operational sex ratios and thus intensive male-male competition for every conception. Paternity analyses matched 21 immature Bornean orangutans with their most likely sire (only 10 of 50 genotyped males) in a natural population. Half of these identified sires had multiple offspring in the study area spread over periods of at least 10 years, despite frequently ranging outside this area. Dominance was a poor predictor of success, but, consistent with female mating tactics to reduce the risk of infanticide, known "sires" tended to have relatively high local presence, which seems to contribute to the males' siring success. The results highlight the importance of large protected areas to enable a natural pattern of dispersal and ranging. The online version contains supplementary material available at 10.1007/s00265-023-03407-6.


Role of cell-bound hemolysin as a pathogenicity factor for Serratia infections.
The hemolytic activities of clinical isolates of Serratia marcescens, of Serratia liquefaciens, and of Escherichia coli strains containing a cloned hemolysin gene of S. marcescens were determined. Hemolysis was induced only by cells and not by spent media. The hemolytically active bacteria induced the release of the leukotriene C4 and of much less leukotriene B4 from polymorphonuclear leukocytes, the release of histamine from rat mast cells, and chemoluminescence of neutrophils. The hemolytic activity was correlated with the response of the leukocytes, but quantitative differences were recorded with regard to the release of the inflammatory mediators. Therefore, other factors in addition to the hemolysin contribute to the stimulation of leukotriene generation and histamine release. It is concluded that the hemolysin via these inflammatory mediators can increase vascular permeability, edema formation, and granulocyte accumulation and thus contributes to the pathogenicity of Serratia species.


Meiotic recombination analyses of individual chromosomes in male domestic pigs (Sus scrofa domestica).
For the first time in the domestic pig, meiotic recombination along the 18 porcine autosomes was directly studied by immunolocalization of MLH1 protein. In total, 7,848 synaptonemal complexes from 436 spermatocytes were analyzed, and 13,969 recombination sites were mapped. Individual chromosomes for 113 of the 436 cells (representing 2,034 synaptonemal complexes) were identified by immunostaining and fluorescence in situ hybridization (FISH). The average total length of autosomal synaptonemal complexes per cell was 190.3 µm, with 32.0 recombination sites (crossovers), on average, per cell. The number of crossovers and the lengths of the autosomal synaptonemal complexes showed significant intra- (i.e. between cells) and inter-individual variations. The distributions of recombination sites within each chromosomal category were similar: crossovers in metacentric and submetacentric chromosomes were concentrated in the telomeric regions of the p- and q-arms, whereas two hotspots were located near the centromere and in the telomeric region of acrocentrics. Lack of MLH1 foci was mainly observed in the smaller chromosomes, particularly chromosome 18 (SSC18) and the sex chromosomes. All autosomes displayed positive interference, with a large variability between the chromosomes.


Analysis with monoclonal antibodies of the molecular and cellular heterogeneity of human high molecular weight melanoma associated antigen.
Monoclonal antibodies (MoAbs) 225.28, 657.9, and 902.5 recognizing distinct epitopes of the human high molecular weight melanoma associated antigen (HMW-MAA) were used to investigate the molecular and cellular heterogeneity of the HMW-MAA synthesized by human melanoma cells. Sequential immunodepletion and immunoprecipitation experiments showed that not all HMW-MAA molecules synthesized by a melanoma cell line express the antigenic determinants recognized by the three monoclonal antibodies. The majority of the HMW-MAA molecules expressed the epitope defined by MoAb 657.9 since this monoclonal antibody depleted the melanoma cell lysate of all antigen molecules recognized by the other two monoclonal antibodies. Depletion with MoAb 902.5 resulted in the removal of a large proportion of the HMW-MAA molecules precipitated by MoAb 657.9. The MoAb 225.28 depleted the cell lysate of only a fraction of the HMW-MAA molecules recognized by MoAb 657.9 and 902.5. Two-dimensional gel electrophoresis and peptide mapping analysis did not detect any significant difference among the HMW-MAA immunoprecipitated by the three monoclonal antibodies. The heterogeneity of the epitopes recognized by the three monoclonal antibodies is, at least partly, due to glycosylation of the antigen molecule, since treatment of melanoma cells with glycosidases differentially affects their ability to bind the three anti-HMW-MAA monoclonal antibodies. Fluorescent activated cell sorting analysis of the melanoma cells showed that the heterogeneity exhibited by the HMW-MAA is not due to the presence of different cell clones in the culture but reflects a differential distribution of epitopes on the HMW-MAA expressed on the surface of individual cells. Immunohistochemical staining of surgically removed benign and malignant lesions of melanocytic origin, of normal tissues, and of malignant lesions has shown a differential tissue distribution of the determinants recognized by the three monoclonal antibodies. Staining of melanoma cell lines and of surgically removed melanoma lesions with combinations of the three monoclonal antibodies did not cause any significant change of the percentage of stained cells but markedly increased the intensity of staining. These results indicate that combinations of monoclonal antibodies to distinct determinants of HMW-MAA can markedly increase the sensitivity of immunohistochemical techniques to detect melanoma cells.


Subjective Aging and Objectively Assessed Hearing Function: A Prospective Study of Older Adults.
Subjective aging is consistently related to a range of health-related outcomes, but little is known about its relationship with sensory functioning. The present prospective study tested whether subjective age and self-perceptions of aging (SPA) are associated with objective hearing function. Participants were 7,085 individuals aged 50-93 years (60% women, mean = 65.15, standard deviation [SD] = 8.71) from the Health and Retirement Study. Measures of subjective age, SPA, and information on demographic factors were obtained in 2008/2010. Objective hearing function was assessed 8 years later in 2016/2018. Furthermore, potential mediating variables (C-reactive protein, body mass index, physical inactivity, and chronic conditions) were assessed in 2012/2014. In regression analyses that accounted for demographic factors, older subjective age and negative SPA were associated with lower hearing acuity 8 years later. In addition, 1 SD older subjective age and negative SPA were related to a 9% and 7% higher likelihood of hearing impairment. Mediation analyses revealed that physical inactivity and chronic conditions partially mediated subjective age and SPA associations with hearing acuity. There was little evidence that the link between subjective aging and hearing was moderated by hearing aids and partial support for a moderating role of age. This study provides new evidence that subjective aging is prospectively related to hearing function. Individuals with older subjective age or negative SPA have unfavorable behavioral and clinical profiles that explain part of their lower hearing function. Individuals' experience with their aging process is a marker of risk for impaired hearing.


Nucleosomal core histones mediate dynamic regulation of poly(ADP-ribose) polymerase 1 protein binding to chromatin and induction of its enzymatic activity.
Poly(ADP-ribose) polymerase 1 protein (PARP1) mediates chromatin loosening and activates the transcription of inducible genes, but the mechanism of PARP1 regulation in chromatin is poorly understood. We have found that PARP1 interaction with chromatin is dynamic and that PARP1 is exchanged continuously between chromatin and nucleoplasm, as well as between chromatin domains. Specifically, the PARP1 protein preferentially interacts with nucleosomal particles, and although the nucleosomal linker DNA is not necessary for this interaction, we have shown that the core histones, H3 and H4, are critical for PARP1 binding. We have also demonstrated that the histones H3 and H4 interact preferentially with the C-terminal portion of PARP1 protein and that the N-terminal domain of PARP1 negatively regulates these interactions. Finally, we have found that interaction with the N-terminal tail of the H4 histone triggers PARP1 enzymatic activity. Therefore, our data collectively suggests a model in which both the regulation of PARP1 protein binding to chromatin and the enzymatic activation of PARP1 protein depend on the dynamics of nucleosomal core histone mediation.


Hyperemesis gravidarum complicated by Wernicke encephalopathy: background, case report, and review of the literature.
Wernicke encephalopathy (WE) is a rare but known complication of severe hyperemesis gravidarum caused by thiamine deficiency. This article presents an unusual case that occurred at our institution and reviews the 48 previously published cases of WE in pregnancy. Considering all the 49 cases, the mean (+/-standard deviation) patients' age was 26.7 +/- 4.9 years, the mean gestational age when WE manifested was 14.3 +/- 3.4 weeks, and the mean duration of vomiting and feeding difficulties was 7.7 +/- 2.8 weeks. Wernicke's classic triad (confusion, ocular abnormalities, and ataxia) manifested in only 46.9% (23 of 49) of the patients. Confusion affected 63.3% (31 of 49) of the patients, ocular signs 95.9% (47 of 49) and symptoms 57.1% (28 of 49), and ataxia 81.6% (40 of 49). Deterioration of consciousness affected 53.1% (26 of 49) of the subjects and memory impairment 61.2% (30 of 49). Complete remission of the disease occurred in only 14 of 49 cases. Symptom resolution required months and permanent impairments were common. The overall pregnancy loss rate, directly (spontaneous fetal loss) and indirectly (planned abortion) attributable to WE, was 47.9% (23 of 49). The diagnosis of WE is clinical and can be rapidly confirmed by magnetic resonance imaging. We emphasize the importance of thiamine supplementation to women with prolonged vomiting in pregnancy, especially before intravenous or parenteral nutrition. We also underline the necessity to promptly replace vitamin B1 when neurologic symptoms and/or signs develop in a patient with hyperemesis gravidarum.


Meaning making in cancer survivors: a focus group study.
Confrontation with a life-threatening disease like cancer can evoke existential distress, which can trigger a search for meaning in people after having survived this disease. In an effort to gain more insight in the meaning making process, we conducted four focus groups with 23 cancer survivors on this topic. Participants responded to questions about experienced meaning making, perceived changes in meaning making after cancer and the perceived need for help in this area. Most frequently mentioned meaning making themes were relationships and experiences. We found that, in general, cancer survivors experienced enhanced meaning after cancer through relationships, experiences, resilience, goal-orientation and leaving a legacy. Some participants, however, also said to have (also) experienced a loss of meaning in their lives through experiences, social roles, relationships and uncertainties about the future. The results indicated that there is a group of cancer survivors that has succeeded in meaning making efforts, and experienced sometimes even more meaning in life than before diagnosis, while there is also a considerable group of survivors that struggled with meaning making and has an unmet need for help with that. The results of this study contribute to develop a meaning centered intervention for cancer survivors.


Scranton Type V Osteochondral Defects of Talus: Does one-stage Arthroscopic Debridement, Microfracture and Plasma Rich in Growth Factor cause the Healing of Cyst and Cessation of Progression to Osteoarthritis?
The study was conducted to evaluate the efficacy of arthroscopic debridement, microfracture and plasma rich in growth factor (PRGF) injection in the management of type V (Scranton) osteochondral lesions of talus and its role in healing the subchondral cyst and cessation of progression of ankle osteoarthritis. This is a prospective case series conducted on patients who were diagnosed with type V osteochondral lesions of talus. All the cases were treated with arthroscopic debridement, microfracture, and PRGF injections. The patients were evaluated for the healing of subchondral cysts and progression of osteoarthritis with radiography (plain radiographs and computerised tomography Scan). Also, the patients' outcome was evaluated with Quadruple Visual Analogue Scale, Ankle Range of Motion, Foot and Ankle Disability Index, Foot and Ankle Outcome Instrument and a Satisfaction Questionnaire. Five male patients underwent arthroscopic debridement, microfracture and PRGF injection for type V osteochondral lesion of talus. The mean age of patients was 27.4 years (19-47 years). All the patients gave history of minor twisting injury. Subchondral cyst healing was achieved in all patients by six months post-surgery. However, four out of five patients had developed early osteoarthritic changes of the ankle by their last follow-up [mean follow-up 29 months (ranged 15-36 months)]. Despite arthritic changes, all the patients reported 'Good' to 'Excellent' results on satisfaction questionnaire and Foot and Ankle Disability Index and could perform their day to day activities including sports. Arthroscopic debridement, microfracture, and PRGF causes healing of the subchondral cyst but does not cause cessation of progression to osteoarthritis of ankle in type V osteochondral defects of talus. However, despite progress to osteoarthritis, patient satisfaction post-procedure is good to excellent at short-term follow-up.


Low-Temperature Plasma Probe Mass Spectrometry for Analytes Separated on Thin-Layer Chromatography Plates: Direct vs Laser Assisted Desorption.
Thin-layer chromatography (TLC) is a widespread technique because it allows fast, simple, and inexpensive analyte separations. In addition, direct analysis of the compounds separated on TLC plates via mass spectrometry (MS) has been shown to provide high sensitivity and selectivity while avoiding time-consuming sample extraction protocols. Here, direct desorption low-temperature plasma-mass spectrometry (LTP-MS) as well as diode laser assisted desorption (LD) LTP-MS are studied for direct spatially resolved analysis of compounds from TLC plates. Qualitative and quantitative characterization of amino acids, pharmaceuticals, and structural isomers were performed. The nature of the TLC plate stationary phase was found to have a significant influence, together with the analyte's characteristics, on the desorption efficiency. Tandem MS is shown to greatly improve the limits of detection (LODs). Direct desorption LTP-MS, without external thermal assisted desorption, demonstrates its best performance with cellulose TLC plates (LODs, 0.01 ng/mm2 to 2.55 ng/mm2) and restricted performance with normal-phase (NP) TLC plates (several analytes without observable signal). LD LTP-MS, with systematic optimization of irradiance and focal point diameter, is shown to overcome the direct-desorption limitations and reach significantly improved LODs with NP TLC plates (up to ×1000 better). In addition, a wide-ranging characterization of amino acid analytical figures of merit with LD LTP-MS shows that LODs from 84 pg/mm2 down to 0.3 pg/mm2 are achieved on NP TLC plates.


N-acetylcysteine protection against the toxicity of cigarette smoke and cigarette smoke condensates in various tissues and cells in vitro.
The protective effect of N-acetylcysteine on the toxicity of tobacco smoke condensates was investigated using different cellular in vitro systems. Cigarette smoke condensates, and the non-volatile and semi-volatile fractions separated from the condensate were used. All three smoke condensate fractions were toxic to isolated rat hepatocytes and lung cells and caused a loss of cell membrane integrity. A rapid depletion of cellular reduced glutathione (GSH) preceded the toxicity. The loss of GSH was due to conjugation of reactive compounds in the condensate fractions and not to oxidation since no increase in oxidized glutathione (GSSG) could be observed. N-acetylcysteine at a concentration of 1 mM protected both from the GSH loss and cell toxicity caused by the condensate fractions. The effect of the tobacco smoke condensate on the colony forming efficiency (CFE) of cultured human bronchial cells was also investigated. Already at concentrations of 50 micrograms/ml the survival decreased to 40% of control and at 100 micrograms/ml almost no cells formed colonies. N-acetylcysteine substantially increased survival when added at 10 mM concentration.


A population-based study of rates of childbirth in recurrence-free female young adult survivors of non-gynecologic malignancies.
Fertility is an important issue for long-term survivors of malignancies developing during reproductive years. We designed a population-based study to investigate childbirth in female young adult survivors of non-gynecologic malignancies. Women 20-34 years diagnosed with non-gynecologic malignancies in Ontario from 1992-1999 who lived at least 5 years recurrence-free were identified using the Ontario Cancer Registry and age matched to 5 randomly selected cancer-free women. Childbirth was determined through hospital discharge data. Time-to-childbirth was compared between survivors and controls using Cox proportional hazard regression for all subjects and stratified by prior childbirth and disease site. 3,285 survivors and 15,118 control women had a median of 12 years observation. 1,194 survivors and 6,049 controls experienced childbirth to the end of observation (March 2011). Overall, survivors experienced a longer time to childbirth than controls (HR 0.92, 95% CI 0.87-0.98), however this was limited to survivors with prediagnosis childbirth (HR 0.76, 95% CI 0.66-0.86). Survivors with no prediagnosis childbirth experienced a similar time to childbirth (HR 1.00, 95% CI 0.93-1.08) as control women. Differences between survivors and controls varied by type of malignancy; notably for those with prediagnosis childbirth, survivors of breast cancer (HR 0.45, 95% CI 0.29-0.68) and Hodgkin Disease (HR 0.57, 95% CI 0.36-0.91) had lower rates of postdiagnosis childbirth than controls. Long-term female young adult survivors of malignancies are less likely than controls to have childbirth after diagnosis; the overall effect is small and is influenced by prediagnosis childbirth and malignancy type.


A comparative analysis of magnetic resonance imaging and radiographic examinations of patients with atypical odontalgia.
To examine (1) the occurrence of magnetic resonance imaging (MRI) signal changes in the painful regions of patients with atypical odontalgia (AO) and (2) the correlation of such findings to periapical bone defects detected with a comprehensive radiographic examination including cone beam computed tomography (CBCT). A total of 20 patients (mean age 52 years, range 34 to 65) diagnosed with AO participated. Mean pain intensity (± standard deviation) was 5.6 ± 1.8 on a 0-10 numerical rating scale, and mean pain duration was 4.3 ± 5.2 years. The inclusion criterion was chronic pain (> 6 months) located in a region with no clear pathologic cause identified clinically or in periapical radiographs. In addition to a clinical examination and a self-report questionnaire, the assessments included radiographic examinations (panoramic, periapical, and CBCT images), and an MRI examination. Changes in MRI signal in the painful region were recorded. Spearman's rank correlation between radiographic and MRI findings was calculated. Eight of the patients (40%) had MRI signal changes in the pain region. The correlation to radiographic periapical radiolucencies was 0.526 (P = .003). Of the eight teeth displaying changes in MRI signal, six showed periapical radiolucency in the radiographs. MRI examination revealed no changes in the painful region in a majority of patients with AO, suggesting that inflammation was not present. MRI findings were significantly correlated to radiographic findings.


DCAlign v1.0: aligning biological sequences using co-evolution models and informed priors.
DCAlign is a new alignment method able to cope with the conservation and the co-evolution signals that characterize the columns of multiple sequence alignments of homologous sequences. However, the pre-processing steps required to align a candidate sequence are computationally demanding. We show in v1.0 how to dramatically reduce the overall computing time by including an empirical prior over an informative set of variables mirroring the presence of insertions and deletions. DCAlign v1.0 is implemented in Julia and it is fully available at https://github.com/infernet-h2020/DCAlign.


Using Neural Circuit Interrogation in Rodents to Unravel Human Speech Decoding.
The neural circuits responsible for social communication are among the least understood in the brain. Human studies have made great progress in advancing our understanding of the global computations required for processing speech, and animal models offer the opportunity to discover evolutionarily conserved mechanisms for decoding these signals. In this review article, we describe some of the most well-established speech decoding computations from human studies and describe animal research designed to reveal potential circuit mechanisms underlying these processes. Human and animal brains must perform the challenging tasks of rapidly recognizing, categorizing, and assigning communicative importance to sounds in a noisy environment. The instructions to these functions are found in the precise connections neurons make with one another. Therefore, identifying circuit-motifs in the auditory cortices and linking them to communicative functions is pivotal. We review recent advances in human recordings that have revealed the most basic unit of speech decoded by neurons is a phoneme, and consider circuit-mapping studies in rodents that have shown potential connectivity schemes to achieve this. Finally, we discuss other potentially important processing features in humans like lateralization, sensitivity to fine temporal features, and hierarchical processing. The goal is for animal studies to investigate neurophysiological and anatomical pathways responsible for establishing behavioral phenotypes that are shared between humans and animals. This can be accomplished by establishing cell types, connectivity patterns, genetic pathways and critical periods that are relevant in the development and function of social communication.


Genome content of uncultivated marine Roseobacters in the surface ocean.
Understanding of the ecological roles and evolutionary histories of marine bacterial taxa can be complicated by mismatches in genome content between wild populations and their better-studied cultured relatives. We used computed patterns of non-synonymous (amino acid-altering) nucleotide diversity in marine metagenomic data to provide high-confidence identification of DNA fragments from uncultivated members of the Roseobacter clade, an abundant taxon of heterotrophic marine bacterioplankton in the world's oceans. Differences in gene stoichiometry in the Global Ocean Survey metagenomic data set compared with 39 sequenced isolates indicated that natural Roseobacter populations differ systematically in several genomic attributes from their cultured representatives, including fewer genes for signal transduction and cell surface modifications but more genes for Sec-like protein secretion systems, anaplerotic CO(2) incorporation, and phosphorus and sulfate uptake. Several of these trends match well with characteristics previously identified as distinguishing r- versus K-selected ecological strategies in bacteria, suggesting that the r-strategist model assigned to cultured roseobacters may be less applicable to their free-living oceanic counterparts. The metagenomic Roseobacter DNA fragments revealed several traits with evolutionary histories suggestive of horizontal gene transfer from other marine bacterioplankton taxa or viruses, including pyrophosphatases and glycosylation proteins.


Synthetic peptides of envelope proteins of two different strains of simian AIDS retrovirus (SRV-1 and SRV-2) represent unique antigenic determinants for serum neutralizing antibodies.
There are at least three distinct serotypes of simian type D retrovirus (SRV) which exhibit extensive serological cross-reactivity, but no cross-reactivity exists at the level of serum neutralizing antibodies. Amino acid sequence analysis and hydrophobicity plots of SRV-1 and SRV-2 envelope proteins were compared in order to identify unique potential antigenic determinants to which respective neutralizing antibodies may be directed. Peptides representing residues 147-162 of SRV-1 and 96-102 of SRV-2 were synthesized and assessed for their immunoreactivity. Free peptide inhibition of strain-specific serum (rhesus) neutralizing antibodies to SRV-1 and SRV-2 was demonstrated using the SRV-1 147-162 peptide and the SRV-2 peptide, 96-102, respectively. Inhibition of serum neutralizing activity by these peptides was also strain-specific, showing no cross-inhibition. SRV-1 147-162 conjugated to a protein carrier and cross-linked to Sepharose beads specifically adsorbed neutralizing antibodies from SRV-1 immune rhesus sera. The antibodies eluted from the immunoadsorbent possessed SRV-1 neutralizing activity, but showed no effect on the infectivity of SRV-2. Peptide SRV-1 147-162 also exhibited the capacity to bind specifically with a mouse monoclonal antibody which neutralizes the infectivity of SRV-1. Mice immunized with a recombinant SRV-1 envelope protein or with whole, inactivated SRV-1 produced antibodies which bound the SRV-1 147-162 conjugate, but not the protein carrier itself. Mouse antibodies to the SRV-1 147-162 conjugate exhibited specific binding with both native SRV-1 and with recombinant SRV-1 envelope protein. These findings provide strong evidence that SRV-1 147-162 and SRV-2 96-102 constitute at least two unique antigenic determinants, or parts thereof, which participate in the strain-specific neutralizing antibody response. Moreover, the findings indicate that the SRV-1 neutralizing antibodies produced by monkeys and at least a certain population of neutralizing antibodies produced by mice recognize the same epitope of SRV-1.


Quantifying predator functional responses under field conditions reveals interactive effects of temperature and interference with sex and stage.
Predator functional responses describe predator feeding rates and are central to predator-prey theory. Originally defined as the relationship between predator feeding rates and prey densities, it is now well known that functional responses are shaped by a multitude of factors. However, much of our knowledge about how these factors influence functional responses is based on laboratory studies that are generally logistically constrained to examining only a few factors simultaneously and that have unclear links to the conditions organisms experience in the field. We apply an observational approach for measuring functional responses to understand how sex/stage differences, temperature and predator densities interact to influence the functional response of zebra jumping spiders on midges under natural conditions. We used field surveys of jumping spiders to infer their feeding rates and examine the relationships between feeding rates, sex/stage, midge density, predator density and temperature using generalized additive models. We then used the relationships supported by the models to fit parametric functional responses to the data. We find that feeding rates of zebra jumping spiders follow some expectations from previous laboratory studies such as increasing feeding rates with body size and decreasing feeding rates with predator densities. However, in contrast to previous results, our results also show a lack of temperature response in spider feeding rates and differential decreases in the feeding rates of females and juveniles with densities of different spider sexes/stages. Our results illustrate the multidimensional nature of functional responses in natural settings and reveal how factors influencing functional responses can interact with one another through behaviour and morphology. Further studies investigating the influence of multiple mechanisms on predator functional responses under field conditions will increase our understanding of the drivers of predator-prey interaction strengths and their consequences for communities and ecosystems.


Metal-responsive transcription factor (MTF-1) and heavy metal stress response in Drosophila and mammalian cells: a functional comparison.
The zinc finger transcription factor MTF-1 (metal-responsive transcription factor-1) is conserved from insects to vertebrates. Its major role in both organisms is to control the transcription of genes involved in the homeostasis and detoxification of heavy metal ions such as Cu2+, Zn2+ and Cd2+. In mammals, MTF-1 serves at least two additional roles. First, targeted disruption of the MTF-1 gene results in death at embryonic day 14 due to liver degeneration, revealing a stage-specific developmental role. Second, under hypoxic-anoxic stress, MTF-1 helps to activate the transcription of the gene placental growth factor (PIGF), an angiogenic protein. Recently we characterized dMTF-1, the Drosophila homolog of mammalian MTF-1. Here we present a series of studies to compare the metal response in mammals and insects, which reveal common features but also differences. A human MTF-1 transgene can restore to a large extent metal tolerance to flies lacking their own MTF-1 gene, both at low and high copper concentrations. Likewise, Drosophila MTF-1 can substitute for human MTF-1 in mammalian cell culture, although both the basal and the metal-induced transcript levels are lower. Finally, a clear difference was revealed in the response to mercury, a highly toxic heavy metal: metallothionein-type promoters respond poorly, if at all, to Hg2+ in mammalian cells but strongly in Drosophila, and this response is completely dependent on dMTF-1.


Gene networks related to the cell death elicited by hyperthermia in human oral squamous cell carcinoma HSC-3 cells.
Local hyperthermia (HT) for various types of malignant tumors has shown promising antitumor effects. To confirm the detailed molecular mechanism underlying cell death induced by HT, gene expression patterns and gene networks in human oral squamous cell carcinoma (OSCC) cells were examined using a combination of DNA microarray and bioinformatics tools. OSCC HSC-3 cells were treated with HT at 44˚C for 90 min or mild hyperthermia (MHT) at 42˚C for 90 min, followed by culturing at 37˚C for 0-24 h. Treatment of cells with HT prevented cell proliferation (62%) and induced cell death (17%), whereas these alterations were not observed in cells treated with MHT. Microarray analysis revealed substantial differences with respect to gene expression patterns and biological function for the two different hyperthermic treatments. Moreover, we identified the temperature-specific gene networks D and H that were obtained from significantly up-regulated genes in the HT and MHT conditions, respectively, using Ingenuity pathway analysis tools. Gene network D, which contains 14 genes such as ATF3, DUSP1 and JUN, was associated with relevant biological functions including cell death and cellular movement. Gene network H, which contains 13 genes such as BAG3, DNAJB1 and HSPA1B, was associated with cellular function and maintenance and cellular assembly and organization. These findings provide a basis for understanding the detailed molecular mechanisms of cell death elicited by HT in human OSCC cells.


In vitro activity of imipenem/relebactam against Pseudomonas aeruginosa isolated from patients with cystic fibrosis.
Pseudomonas aeruginosa is a common multidrug-resistant pathogen in patients with cystic fibrosis (CF). The in vitro activity of imipenem/relebactam and imipenem was compared with other antipseudomonal antibiotics against 105 isolates from patients with CF from three US hospitals. Imipenem/relebactam, imipenem, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam susceptibilities were 77%, 55%, 58%, 90%, and 92%, respectively. Relebactam potentiates imipenem against CF P. aeruginosa by fourfold leading imipenem/relebactam to retain susceptibility against most isolates in this cohort.


The contribution of frictional torque to loosening at the cement-bone interface in Tharies hip replacements.
We evaluated the results in a series of 170 osteoarthrotic hips (156 patients) at a median of 10.0 years (range, 3.0 to 16.4 years) after a Tharies resurfacing arthroplasty performed with cement. Our purpose was to assess the role of frictional torque in loosening at the cement-bone interface. The hips were divided into three groups on the basis of the diameter of the bearing surface: small (thirty-six, thirty-nine, or forty-three millimeters), medium (forty-seven millimeters), and large (fifty-one or fifty-four millimeters). Comparisons were made with Kaplan-Meier survivorship analysis, with stepwise discriminant analysis of risk factors for aseptic loosening. Revision for aseptic loosening was the end point for survivorship analysis. Despite higher frictional torques due to the increased diameter of the bearing surface and the increased average load, the larger prostheses survived significantly longer than the smaller ones (p=0.002). Stepwise covariate discriminant analysis indicated that the size of the bearing surface was the only factor identified that significantly affected survival. In six patients who had had a bilateral surface replacement with a component of a different size in each hip, the smaller prosthesis always failed first (p=0.001), at an average of seventy-seven months; the larger prosthesis failed at an average of 113 months. Nine patients had had a bilateral replacement with components of the same size, and there was no significant difference in the durations of survival of the two prostheses. Analysis of radiographs and retrieved specimens indicated that, regardless of the size of the component, the mechanism of loosening on both the acetabular and the femoral side of this so-called double-cup replacement was progressive resorption of bone induced by polyethylene wear particles that compromised the fixation of the components. More time was required for the process to disrupt++ the larger fixation area of the larger components. These data indicate that frictional torque was not the primary factor in the loosening of these prostheses with a large bearing surface and that higher friction and frictional torques can be tolerated if the generation of wear debris is sufficiently limited. These findings may be important as alternatives to polyethylene bearing surfaces are investigated.


Thyroid cancer: is the incidence still increasing?
The objective of this study was to define the epidemiology of thyroid cancer in our regional population and compare results with Surveillance, Epidemiology, and End RESULTS (SEER) Program cancer registry trends. Thyroid cancer cases diagnosed between 1990 and 2000 were identified in the Florida Cancer Data System (FCDS). Overall, gender-specific, age-specific, and stage-specific incidence rates were calculated. All rates are per 100,000 and age-adjusted to the 2000 U.S. standard population. Estimated Annual Percent Change (EAPC) was calculated with a linear least-squares model. Patients with thyroid cancer (n = 8603) were identified in the FCDS registry. Age-adjusted incidence rates increased from 4.2 per 100,000 to 7 per 100,000 in 2000. The EAPC for this period was 5.5% (P < .001). The SEER incidence rates increased from 7.9 to 10.2 per 100,000, and the EAPC was 3.7% (P < .05). Analysis of gender-specific incidence rates showed increases from 6 and 2.2 per 100,000 in 1990 to 10.1 and 3.8 per 100,000 in 2000 among females and males, respectively, with EAPCs of 5.9% (females) and 4.5% (males) (P < .001). With stratification by age group, the highest incidence rates were 9 per 100,000 in the group aged 65 to 84 years and 8.4 per 100,000 in the group aged 45 to 64 years. Thyroid cancer incidence rates in Florida almost doubled over the 1990-2000 period and are concordant with SEER trends. Etiologic studies addressing temporal changes in reproductive factors, more intensive diagnostic activities, and changes in histological criteria are warranted.


Role of voltage-sensitive release mechanism in depression of cardiac contraction in myopathic hamsters.
We investigated excitation-contraction (EC) coupling in isolated ventricular myocytes from prehypertrophic cardiomyopathic (CM) hamster hearts. Conventional and voltage-clamp recordings were made with high-resistance microelectrodes, and cell shortening was measured with a video-edge detector at 37 degrees C. Contractions were depressed in myocytes from CM hearts, whether they were initiated by action potentials or voltage-clamp steps. As in guinea pig and rat, contraction in hamster myocytes could be triggered by a voltage-sensitive release mechanism (VSRM) or Ca(2+)-induced Ca(2+) release (CICR). Selective activation of these mechanisms demonstrated that the defect in EC coupling was primarily caused by a defect in the VSRM. However, activation and inactivation properties of the VSRM were not altered. When the VSRM was inhibited, the remaining contractions induced by CICR exhibited identical bell-shaped contraction voltage relations in normal and CM myocytes. Inward Ca(2+) current was unchanged. Thus a defect in the VSRM component of EC coupling precedes the development of hypertrophy and failure in CM hamster heart.


Practical approach for pretreatment verification of IMRT with flattening filter free(FFF) beams using Varian Portal Dosimetry.
Patient-specific pretreatment verification of intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) is strongly recommended for all patients in order to detect any potential errors in treatment planning process and machine deliverability, and is thus performed routinely in many clinics. Portal dosimetry is an effective method for this purpose because of its prompt setup, easy data acquisition, and high spatial resolution. However, portal dosimetry cannot be applied to IMRT or VMAT with flattening filter-free (FFF) beams because of the high dose-rate saturation effect of the electronic portal imaging device (EPID). In our current report, we suggest a practical QA method of expanding the conventional portal dosimetry to FFF beams with a QA plan generated by the following three steps: 1) replace the FFF beams with flattening filtered (FF) beams of the same nominal energy; 2) reduce the dose rate to avoid the saturation effect of the EPID detector; and 3) adjust the total MU to match the gantry and MLC leaf motions. Two RapidArc plans with 6 and 10 MV FFF beams were selected, and QA plans were created by the aforementioned steps and delivered. The trajectory log files of TrueBeam obtained during the treatment and during the delivery of QA plan were analyzed and compared. The maximum discrepancies in the expected trajectories between the treatment and QA plans were within 0.002 MU for the MU, 0.06° for the motion of gantry rotation, and 0.006 mm for the positions of the MLC leaves, indicating much higher levels of accuracy compared to the mechanical specifications of the machine. For further validation of the method, direct comparisons of the delivered QA FF beam to the treatment FFF beam were performed using film dosimetry and show that gamma passing rates under 2%/2 mm criteria are 99.0%-100% for the all four arc beams. This method can be used on RapidArc plans with FFF beams without any additional procedure or modifications on the conventional portal dosimetry of IMRT and is, therefore, a practical option for routine clinical use.


Health-care league tables in the United Kingdom.
There is a global search for performance indicators for health services as a basis for quality improvement, external assessment, management control and public accountability and information. This requires agreement on what constitutes good performance as perceived by a disparate range of potential users, and on what aggregated or tracer data faithfully reflect policy objectives. To these challenges are added the technical problems of collating comparisons which are complete, accurate, timely and statistically valid, as well as behavioural problems of their interpretation and use. Examples are given of the Patients' Charter (National Health Service in England) and the Scottish outcome indicators. This experience from the UK may well have some relevance in other countries.


Discrimination of speed in 5-year-olds and adults: are children up to speed?
We compared thresholds for discriminating changes in speed by 5-year-olds and adults for two reference speeds: 1.5 and 6 degrees s(-1). Both adults and 5-year-olds were more sensitive to changes from the faster than from the slower reference speed. Five-year-olds were less sensitive than adults at both reference speeds but significantly more immature at the slower (1.5 degrees s(-1)) than at the faster (6 degrees s(-1)) reference speed. The findings suggest that the mechanisms underlying speed discrimination are immature in 5-year-olds, especially those that process slower speeds.


Cephalic version by moxibustion for breech presentation.
Moxibustion (a type of Chinese medicine which involves burning a herb close to the skin) to the acupuncture point Bladder 67 (BL67) (Chinese name Zhiyin), located at the tip of the fifth toe, has been proposed as a way of correcting breech presentation. As caesarean section is often suggested for breech babies due to the potential difficulties during labour, it is preferable to turn the baby before labour starts. To examine the effectiveness and safety of moxibustion on changing the presentation of an unborn baby in the breech position, the need for external cephalic version (ECV), mode of birth, and perinatal morbidity and mortality for breech presentation. We searched the Cochrane Pregnancy and Childbirth Group trials register (30 August 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2004), MEDLINE (1966 to March 2004), EMBASE (1980 to March 2004), CINAHL (1982 to March 2004), MIDIRS (1982 to March 2004), CISCOM (9 March 2004) and bibliographies of relevant papers. The inclusion criteria were published and unpublished randomised controlled trials comparing moxibustion (either alone or in combination with acupuncture) with a control group (no moxibustion), or other methods (e.g. external cephalic version, acupuncture) in women with a singleton breech presentation. Both authors assessed eligibility and quality of trials independently. The outcome measures were baby's presentation at birth, need for external cephalic version, mode of birth, perinatal morbidity and mortality, maternal complications and maternal satisfaction, and adverse events. Three trials involving a total of 597 women were included. Due to differences in interventions and sample size it was not appropriate to perform a meta-analysis for the main outcome. Only one trial reported on other outcome measures relevant to this review. Moxibustion reduced the need for ECV (relative risk (RR) 0.47, 95% confidence interval (CI) 0.33 to 0.66) and resulted in decreased use of oxytocin before or during labour for women who had vaginal deliveries (RR 0.28, 95% CI 0.13 to 0.60). There is insufficient evidence to support the use of moxibustion to correct a breech presentation. Moxibustion may be beneficial in reducing the need for ECV, and decreasing the use of ocytocin, however there is a need for well-designed randomised controlled trials to evaluate moxibustion for breech presentation which report on clinically relevant outcomes as well as the safety of the intervention.


P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR.
The biochemistry of foreign compound metabolism and the roles played by individual cytochrome P450 (CYP) enzymes in drug metabolism and in the toxification and detoxification of xenochemicals prevalent in the environment are important areas of molecular pharmacology and toxicology that have been widely studied over the past decade. Important advances in our understanding of the mechanisms through which foreign chemicals impact on these P450-dependent metabolic processes have been made during the past 2 years with several key discoveries relating to the mechanisms through which xenochemicals induce the expression of hepatic P450 enzymes. Roles for three "orphan" nuclear receptor superfamily members, designated CAR, PXR, and PPAR, in respectively mediating the induction of hepatic P450s belonging to families CYP2, CYP3, and CYP4 in response to the prototypical inducers phenobarbital (CAR), pregnenolone 16alpha-carbonitrile and rifampicin (PXR), and clofibric acid (PPAR) have now been established. Two other nuclear receptors, designated LXR and FXR, which are respectively activated by oxysterols and bile acids, also play a role in liver P450 expression, in this case regulation of P450 cholesterol 7alpha-hydroxylase, a key enzyme of bile acid biosynthesis. All five P450-regulatory nuclear receptors belong to the same nuclear receptor gene family (family NR1), share a common heterodimerization partner, retinoid X-receptor (RXR), and are subject to cross-talk interactions with other nuclear receptors and with a broad range of other intracellular signaling pathways, including those activated by certain cytokines and growth factors. Endogenous ligands of each of those nuclear receptors have been identified and physiological receptor functions are emerging, leading to the proposal that these receptors may primarily serve to modulate hepatic P450 activity in response to endogenous dietary or hormonal stimuli. Accordingly, P450 induction by xenobiotics may in some cases lead to a perturbation of endogenous regulatory circuits with associated pathophysiological consequences.


Serum leptin levels in acute protein deprivation.
Protein energy malnutrition (PEM) induces a host neuroendocrine response, reflected by significant elevations in circulating glucocorticoid levels and associated with metabolic and immune dysfunction. Leptin regulates food intake and body mass and has a significant impact on the hypothalamic-pituitary-adrenal axis (HPA). We hypothesized that leptin may be altered by and may play an important role in regulating the effects of PEM. Female Balb/c mice were used. In experiment 1, mice were pair-fed either a protein-free (0% casein) or control (24% casein) diet for 7 days. In experiment 2, mice were implanted with either a placebo or corticosterone-releasing pellet and fed the control diet for 7 days. In experiment 3, adrenalectomized mice were pair-fed either the protein-free or control diet for 7 days. Serum corticosterone and leptin levels were measured in all experiments. PEM caused significant reductions in food intake, body weight, and total body fat, but not lean body mass. Serum corticosterone and leptin levels were significantly greater in mice fed the protein-free diet. Subcutaneous implantation of a corticosterone pellet in mice fed the control diet resulted in a significantly elevated serum leptin level compared with placebo-implanted controls. Bilateral adrenalectomy partially blunted the increased serum leptin in PEM. Leptin may be an important mediator of weight loss and decreased food intake in PEM. Elevated serum leptin in PEM may be secondary to elevated serum corticosterone, with other factors inherent in the host response to protein restriction also contributing to elevated serum leptin.


The role of BATF2 deficiency in immune microenvironment rearrangement in cervical cancer - New biomarker benefiting from combination of radiotherapy and immunotherapy.
Despite the significant progress in immunotherapy for certain cancers, including cervical cancer, most patients remain unresponsive or derive limited benefits from combined radiotherapy and chemotherapy. The factors underlying treatment resistance are unknown and there are few reliable predictive biomarkers. BATF2 is a member of the basic leucine zipper transcription factor family and is involved in immune response and immune cell development. However, the role of BATF2 in the immune microenvironment of patients with cervical cancer after radiotherapy remains unclear. In this study, immunohistochemistry and multicolour immunofluorescence analyses of patient tumor samples were used to assess BATF2 expression. We found that cervical cancer patients with high BATF2 expression had higher infiltration levels of CD4+ T cells, CD8+ T cells, and macrophages within the tumor than those with low expression levels. Furthermore, BATF2 expression was positively correlated with the prognosis of patients after concurrent chemoradiotherapy. A wild-type mouse model with BATF2-knockdown U14 cell-derived subcutaneous tumors and a Batf2-/- mouse model with wild-type U14 cell-derived subcutaneous tumors were used to assess CD8+ T cell infiltration and function. As expected, the knockdown of BATF2 in the U14 cell line substantially promoted tumor growth, which was mediated by a reduction in CD8+ T cell infiltration and antitumor function in vivo. Additionally, the Batf2-/- mouse model demonstrated that host BATF2 is also involved in controlling tumor growth. Furthermore, the combination of radiotherapy and anti-PD-1 therapy showed synergistic antitumour effects. These findings collectively suggest that BATF2 may serve as a potent positive regulator of the tumor immune microenvironment of cervical cancer after radiotherapy, and has the potential to be a prognostic biomarker to guide the application of a combination of radiotherapy and immunotherapy.


The limits of conscientious objection to abortion in the developing world.
The South African Choice on Termination of Pregnancy Act 92 of 1996 gives women the right to voluntary abortion on request. The reality factor, however, is that five years later there are still more 'technically illegal' abortions than legal ones. Amongst other factors, one of the main obstacles to access to this constitutionally enshrined human right is the right to conscientious objection/refusal. Although the right to conscientious objection is also a basic human right, the case of refusal to provide abortion services on conscientious objection grounds should not be seen as absolute and inalienable, at least in the developing world. In the developed world, where referral to another service provider is for the most part accessible, a conscientious objector to abortion does not really put the abortion seeker's life at risk. The same cannot be said in developing countries even when abortion is decriminalised. This is because referral procedures are fraught with major obstacles. Therefore, it is argued that the right to conscientious objection to abortion should be limited by the circumstances in which the request for abortion arises.


High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. Children's Cancer Group.
Medulloblastoma is a highly lethal disease when it recurs. Very few patients survive with conventional treatment. This study evaluated the use of high-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue (ASCR) in patients with recurrent medulloblastoma. Chemotherapy consisted of carboplatin 500 mg/m2 (or area under the curve = 7 mg/mL x min via Calvert formula) on days -8, -7, and -6; and thiotepa 300 mg/m2 and etoposide 250 mg/m2 on days -5, -4, and -3; followed by ASCR on day 0. In addition to the study-prescribed therapy, 21 patients received other treatment: neurosurgical resection in seven, conventional chemotherapy in 17, and external-beam irradiation in 11 cases. Twenty-three patients with recurrent medulloblastoma, aged two to 44 years (median, 13 years) at ASCR, were treated. Three patients died of treatment-related toxicities within 21 days of ASCR; multiorgan system failure in two, and Aspergillus infection with venoocclusive disease in one. Seven of 23 patients (30%) are event-free survivors at a median of 54 months post-ASCR (range, 24 to 78 months). Kaplan-Meier estimates of event-free (EFS) and overall survival are 34% +/- 10% and 46% +/- 11%, respectively, at 36 months post-ASCR. This strategy may provide long-term survival for some patients with recurrent medulloblastoma.


[Prognostication of the outcome of surgical treatment of hemorrhagic strokes using a computer].
A new mathematical method is suggested for making the prognosis of the results of surgery for haemorrhagic strokes due to essential hypertension and atherosclerosis. Twenty-two signs characterizing the patient's state are fed into the computer trained on the basis of 124 case reports of patients, both surviving and dying after surgery. The computer operating in accordance with the "Kopa-3" programme works out a vital prognosis for both the medicamental and surgical treatment. The prognosis proved correct in 90% of the cases. The described method permits an objective determination of the indications for surgery in hemorrhagic stroke.


Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study.
The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.


Ulnar neuropathy caused by an accessory abductor digiti minimi muscle.
Peripheral neuropathies of the ulnar nerve at various locations in the upper extremity are common, but compression of the ulnar nerve at the level of the wrist due to an anomalous muscle is rare, though reported in the literature. Three cases of an abnormal abductor digiti minimi origin were first reported by Wood in 1868, but no mention was made of an associated ulnar neuropathy. To data, there have been 8 reported cases of an anomalous abductor digiti minimi, with sensory or motor abnormalities of the ulnar nerve the most common presentation. This case report describes a patient who had subjective paresthesiae in the ulnar nerve distribution for 2 years. He was found, at exploration, to have an anomalous muscle belly originating proximally from the deep forearm fascia with insertion into the abductor digiti minimi. We present the case, discuss the spectrum of compression neuropathies of the ulnar nerve at the wrist, and a review of the occurrence of anomalous muscles responsible.


Structural Correlates of Reading the Mind in the Eyes in Autism Spectrum Disorder.
Behavioral studies have shown that individuals with autism spectrum disorder (ASD) have impaired ability to read the mind in the eyes. Although this impairment is central to their social malfunctioning, its structural neural correlates remain unclear. To investigate this issue, we assessed Reading the Mind in the Eyes Test, revised version (Eyes Test) and acquired structural magnetic resonance images in adults with high-functioning ASD (n = 19) and age-, sex- and intelligence quotient-matched typically developing (TD) controls (n = 19). On the behavioral level, the Eyes Test scores were lower in the ASD group than in the control group. On the neural level, an interaction between group and Eyes Test score was found in the left temporoparietal junction (TPJ). A positive association between the Eyes Test score and gray matter volume of this region was evident in the control group, but not in the ASD group. This finding suggests that the failure to develop appropriate structural neural representations in the TPJ may underlie the impaired ability of individuals with ASD to read the mind in the eyes. These behavioral and neural findings provide support for the theories that impairments in processing eyes and the ability to infer others' mental states are the core symptoms of ASD, and that atypical features in the social brain network underlie such impairments.


Bacterial diversity of bacteriomes and organs of reproductive, digestive and excretory systems in two cicada species (Hemiptera: Cicadidae).
Cicadas form intimate symbioses with bacteria to obtain nutrients that are scarce in the xylem fluid they feed on. The obligate symbionts in cicadas are purportedly confined to specialized bacteriomes, but knowledge of bacterial communities associated with cicadas is limited. Bacterial communities in the bacteriomes and organs of reproductive, digestive and excretory systems of two cicada species (Platypleura kaempferi and Meimuna mongolica) were investigated using different methods, and the bacterial diversity and distribution patterns of dominant bacteria in different tissues were compared. Within each species, the bacterial communities of testes are significantly different from those of bacteriomes and ovaries. The dominant endosymbiont Candidatus Sulcia muelleri is found not only in the bacteriomes and reproductive organs, but also in the "filter chamber + conical segment" of both species. The transmission mode of this endosymbiont in the alimentary canal and its effect on physiological processes merits further study. A novel bacterium of Rhizobiales, showing ~80% similarity to Candidatus Hodgkinia cicadicola, is dominant in the bacteriomes and ovaries of P. kaempferi. Given that the genome of H. cicadicola exhibits rapid sequence evolution, it is possible that this novel bacterium is a related endosymbiont with beneficial trophic functions similar to that of H. cicadicola in some other cicadas. Failure to detect H. cicadicola in M. mongolica suggests that it has been subsequently replaced by another bacterium, a yeast or gut microbiota which compensates for the loss of H. cicadicola. The distribution of this novel Rhizobiales species in other cicadas and its identification require further investigation to help establish the definition of the bacterial genus Candidatus Hodgkinia and to provide more information on sequence divergence of related endosymbionts of cicadas. Our results highlight the complex bacterial communities of cicadas, and are informative for further studies of the interactions and co-evolution of insect-microbial symbioses in Cicadoidea.


Population study in the high natural background radiation area in Kerala, India.
A comprehensive survey of the population exposed to high-level natural radiation is presented. The population living in Karunagappally taluk in Kerala, India, presents a unique opportunity for studies on the health effects of chronic exposure to low-level radiation. The environmental radiation emanates largely from the thorium deposited mostly along coastal areas. In certain locations on the coast, it is as high as 70 mGy/year and on average is 7.5 times the level seen in interior areas. Using portable scintillometers, radiation levels in more than 66,306 houses were measured; outside levels were also measured in the same house compound. Of the total population of 400,000, 100,000 lived in areas with high natural radiation. Information on lifestyle, socio-demographic features, occupation, housing, residence history, and tobacco and alcohol use was obtained by house-to-house visits and enumeration of every resident individual. A population cancer registry system has been established to obtain cancer incidence rates. In this preliminary analysis, there is no evidence that cancer occurrence is consistently higher because of the levels of external gamma-radiation exposure in the area. Further dosimetry-level studies are needed along with biological studies. Studies of soil, thoron-in-breath, and the radon-thoron levels in houses are ongoing, and further case-control analyses are continuing.


Worker allometry in relation to colony size and social form in the fire ant Solenopsis invicta.
Workers of the polymorphic fire ant Solenopsis invicta Buren (Hymenoptera: Formicidae) show modest changes of shape with increases in body size. These shape changes (allometries) have been described only for workers taken from mature colonies of the monogyne social form. For the study reported here, workers were collected from small and large monogyne and large polygyne colonies for tests of the effects of colony size and social form on allometry. The differential growth of body parts in relation to total body growth was determined by measurement of all major body parts and regression of the logs of these measurements, or their ratios, on the log of the body size. The slopes of these regressions defined the allometric relationships, and the slopes for these three types of colonies were compared for determination of the influence of colony size and social form on allometric rules. Most allometric constants did not differ with colony size or social form, but head shape, relative antennal size, and alinotum shape did. For a given worker size, heads of workers from small monogyne colonies or from polygyne colonies were narrower above the eyes. Antennae of workers from large monogyne colonies were relatively shorter than those from small monogyne or polygyne colonies (which did not differ). Alinotum heights of small workers from small monogyne colonies were greater than those from large monogyne or polygyne colonies (which were isometric and did not differ). These observed differences in allometric constants suggest that the relative growth rules are not completely determined by worker body size but are affected by colony size and social form. These differences are discussed in light of the growth of imaginai discs under conditions of fixed resources.


An optical probe possessing upconversion luminescence and Hg(2+)-sensing properties.
A Hg(2+)-selective chromophoric upconversion nanosystem is achieved by covalently grafting Rhodamine B hydrazide (RB-hydrazide) onto upconversion luminescent nanorod core-shell structures. The prepared β-NaYF4 nanorods are coated with silica and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDAX), Fourier-transform infrared spectroscopy (FTIR), and photoluminescence spectra. Under 980 nm excitation, the upconversion luminescence is sensitive towards Hg(2+) because RB-hydrazide-Hg can efficiently absorb green upconversion emission. The prepared nanocomposites exhibit high sensitivity and selectivity towards Hg(2+) over other metal ions. These results indicate that this nanosystem could be developed as a promising fluorescence probe for detecting Hg(2+) ions.


A HPLC-based glycoanalytical protocol allows the use of natural O-glycans derived from glycoproteins as substrates for glycosidase discovery from microbial culture.
Many disorders are characterised by changes in O-glycosylation, but analysis of O-glycosylation has been limited by the availability of specific endo- and exo-glycosidases. As a result chemical methods are employed. However, these may give rise to glycan degradation, so therefore novel O-glycosidases are needed. Artificial substrates do not always identify every glycosidase activity present in an extract. To overcome this, an HPLC-based protocol for glycosidase identification from microbial culture was developed using natural O-glycans and O-glycosylated glycoproteins (porcine stomach mucin and fetuin) as substrates. O-glycans were released by ammonia-based β-elimination for use as substrates, and the bacterial culture supernatants were subjected to ultrafiltration to separate the proteins from glycans and low molecular size molecules. Two bacterial cultures, the psychrotroph Arthrobacter C1-1 and a Corynebacterium isolate, were examined as potential sources of novel glycosidases. Arthrobacter C1-1 culture contained a β-galactosidase and N-acetyl-β-glucosaminidase when assayed using 4-methylumbelliferyl substrates, but when defucosylated O-glycans from porcine stomach mucin were used as substrate, the extract did not cleave β-linked galactose or N-acetylglucosamine. Sialidase activity was identified in Corynebacterium culture supernatant, which hydrolysed sialic acid from fetuin glycans. When both culture supernatants were assayed using the glycoproteins as substrate, neither contained endoglycosidase activity. This method may be applied to investigate a microbial or other extract for glycosidase activity, and has potential for scale-up on high-throughput platforms.


Treatment of Ulnar Collateral Ligament Injuries and Superior Labral Tears by Major League Baseball Team Physicians.
To determine practice patterns of Major League Baseball (MLB) team orthopaedic surgeons in addressing the controversial topics of ulnar collateral ligament (UCL) tears, type II SLAP tears, and partial-thickness rotator cuff tear. Seventy-four MLB team orthopaedic surgeons were surveyed via an online survey system. A 14-question survey was used to assess surgeon experience, technique, and graft choice for UCL reconstruction (UCLR), treatment of type II SLAP tears, and other common pathologic conditions. Thirty team orthopaedic surgeons (41%) responded (mean experience as team physicians: 9.37 ± 6.33 years). Seventeen (56.7%) surgeons use the docking technique for UCLR whereas 20% use the modified Jobe technique. Nineteen (63.3%) use palmaris longus autograft in UCLR. Overall, 28 (93.3%) do not routinely perform elbow arthroscopy or perform an obligatory transposition of the ulnar nerve in patients without preoperative ulnar nerve symptoms. Twenty-eight (93.3%) would repair a type II SLAP tear, whereas only 1 (3.3%) would debride the tear. No surgeon would perform a concomitant biceps tenodesis, either open or arthroscopic. Most MLB team orthopaedic surgeons perform a UCLR using the docking technique with a palmaris longus autograft without concomitant elbow arthroscopy or obligatory transposition of the ulnar nerve. The overwhelming majority of these surgeons would also treat an operative type II SLAP tear with a SLAP repair. The number of UCLRs and SLAP repairs performed on MLB pitchers has significantly increased over the past 10 years. To properly treat these conditions in elite, college, and recreational athletes, it is important to understand how the surgeons who take care of the most elite-level athletes treat them, and how they are able to reproducibly attain excellent outcomes. This study shows how these common shoulder and elbow injuries are treated by those surgeons who care for the most elite overhead-throwing athletes in the world.


Natural history of NASH and HCC.
Widespread unhealthy dietary habits associated with a sedentary lifestyle have made NAFLD the most frequent chronic liver disease worldwide, with a global prevalence of ~25%. Although NAFLD is mainly considered to be a benign disease, it can progress to severe liver fibrosis and hepatocellular carcinoma (HCC), with the latter found in non-cirrhotic livers in about 40% of cases. Factors favouring the progression of liver disease in NAFLD are only partially understood. Male sex, older age and Caucasian ethnicity have frequently been identified as factors accelerating the progression of fibrosis in NAFLD, although data are not consistent. Host genetic variants appear to be very important, especially in the gene coding for the patatin-like phospholipase domain-containing 3 (PNPLA3), and they may also play a role in the development of HCC, independent of activity and the extent of liver damage. However, the most important factors affecting disease progression are found in the metabolic syndrome, that is, obesity, type 2 diabetes and arterial hypertension. This mini-review will discuss the contribution of these factors to NAFLD-associated morbidity, emphasizing the importance of preventive measures such as physical activity and weight control in view of the current pandemic of the metabolic syndrome.


An Asymmetric Organocatalytic Quadruple Cascade to Tetraaryl-Substituted 2-Azabicyclo[3.3.0]octadienones.
A new asymmetric organocatalytic three-component quadruple cascade of α-ketoamides with α,β-unsaturated aldehydes is described. The reaction is catalyzed by the (S)-diphenylprolinol TMS ether catalyst and proceeds via an aza-Michael/aldol condensation/vinylogous Michael/aldol condensation sequence to yield tetraaryl-substituted 2-azabicyclo[3.3.0]octadienone derivatives. The cascade products are obtained with good to very good yields (34-71%), virtually complete diastereoselectivities (>20:1), and very good enantioselectivities (84-97%).


Evaluation of techniques for the diagnosis of Strongyloides stercoralis in human immunodeficiency virus (HIV) positive and HIV negative individuals in the city of Itajaí, Brazil.
Human immunodeficiency virus (HIV) and intestinal parasites are common in Brazil. Previous studies have shown that infection with Strongyloides stercoralis is frequently associated with HIV infection. Strongyloidiasis is difficult to diagnosis and stool examination with conventional techniques fails to detect the helminth larvae. We made a prospective study, to test the efficacy of the agar plate technique to detect S. stercoralis in 211 HIV-positive patients and 213 HIV-negative patients in the city of Itajaí, Brazil, between September 2001 and June 2002. The feces samples of these patients were processed and analyzed according to the following methods: Lutz, formalin ethyl acetate, Baermann, Harada-Mori and agar plate culture. HIV-positive patients were more frequently infected by S. stercoralis (odds ratio= 5,.687). Among the methods used on fecal specimens, the larvae of S. stercoralis were most efficiently detected by the agar plate (69.7%) method, followed by the Baermann and the formalin ethyl acetate methods (48.5%) (P=0.01), Lutz (42.4%) (P=0.01), and Harada-Mori culture (24%) (P=0.001). Therefore agar plate culture is the most efficient method for the detection of S. stercoralis larvae and this technique should be the test of choice, especially in immunocompromised patients.


Neutralizing human antibodies to varicella-zoster virus (VZV) derived from a VZV patient recombinant antibody library.
Varicella-zoster virus (VZV), the causative agent of chickenpox and herpes zoster, can be life-threatening in prematurely born children and in children with immune defects or who are under immunosuppressive treatment. Therefore agents for passive immunization, such as VZV-specific immunoglobulin preparations (VZIG) derived from convalescent plasma, are crucial in the prophylaxis of VZV infection. This study describes the isolation of human VZV-neutralizing recombinant antibodies. A human single-chain variable fragment (scFv) phage display library was generated from RNA extracted from peripheral blood lymphocytes of a convalescent varicella patient. Specific phage antibodies were selected against VZV-infected human fibroblasts, and eight unique clones were further expressed as soluble scFv in Escherichia coli. They all showed binding characteristics to varicella antigens with affinities in the K(D) range 0.1-0.2 muM. Two of the scFv antibodies, VZV4 and VZV5, showed dose-dependent in vitro neutralization of VZV. VZV39 also showed a neutralizing effect as scFv, an effect that was increased 4000-fold by conversion into IgG and was further increased by the addition of complement. This is possibly the first time that monovalent scFv antibodies have been shown to neutralize VZV in vitro. This finding will have an impact on the production of new prophylactic antibodies, as such antibody fragments can be cost-effectively produced in E. coli. The antibodies isolated bind both complement-dependent and -independent epitopes for neutralization, thus they may prove useful tools for the study of VZV virulence mechanisms.


Does orally administered doxycycline reach the tear film?
Orally administered doxycycline, a broad-spectrum antibiotic, is an established treatment for ocular surface diseases, particularly rosacea, meibomian gland dysfunction and recurrent epithelial cell erosion. In recent times, its efficacy in treating these diseases has been ascribed to an ability to inhibit matrix metalloproteinase (MMP) activity and both MMP and interleukin-1 (IL-1) synthesis. Since these functions are concentration-dependent, the aim of this project was to determine whether sufficient doxycycline reached the tear film to fulfil these roles in vivo. Doxycycline was extracted with 1-butanol from tear and blood plasma samples obtained from patients with ocular surface disease and healthy individuals and quantified spectrophotometrically. The MMPs present in the patients tear films before and during doxycycline treatment were analysed zymographically. The quantity of doxycycline detected in the blood plasma samples of patients undergoing treatment ranged from 1.83 to 13.18 microM. Although doxycycline was not detected in their tear samples, the treatment caused the disappearance of the MMPs symptomatic of disease progression. The inability to detect doxycycline in the tear film of patients undergoing treatment indicates that doxycycline does not directly inhibit MMP activity or the synthesis/secretion of these proteases and IL-1 from corneal epithelial cells.


The role of LOXL2 induced by glucose metabolism-activated NF-κB in maintaining drug resistance through EMT and cancer stemness in gemcitabine-resistant PDAC.
Gemcitabine is considered a standard treatment for pancreatic cancer, but developing drug resistance greatly limits the effectiveness of chemotherapy and increases the rate of recurrence. Lysyl oxide-like 2 (LOXL2) is highly expressed in pancreatic cancer and is involved in carcinogenesis and EMT regulation. However, studies on the role of LOXL2 in drug resistance are limited. Here, we investigated the mechanism of LOXL2 induction and the effect of LOXL2 on EMT and CSC in gemcitabine-resistant pancreatic cancer. Glucose metabolism was activated in gemcitabine-resistant pancreatic cancer cells, and NF-κB signaling was regulated accordingly. Activated NF-κB directly induces transcription by binding to the promoters of LOXL2 and ZEB1. The EMT process was significantly inhibited by the coregulation of ZEB1 and LOXL2. In addition, LOXL2 inhibition reduced the expression of cancer stemness markers and stemness by regulating MAPK signaling activity. LOXL2 inhibits tumor growth of gemcitabine-resistant pancreatic cancer cells and increases the sensitivity to gemcitabine in mouse models. KEY MESSAGES: We identified a specific mechanism for inducing LOXL2 overexpression in gemcitabine-resistant pancreatic cancer. Taken together, our results suggest LOXL2 has an important regulatory role in maintaining gemcitabine resistance and may be an effective therapeutic target to treat pancreatic cancer.


Whole genome analysis of a livestock-associated methicillin-resistant Staphylococcus aureus ST398 isolate from a case of human endocarditis.
Recently, a new livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) Sequence Type 398 (ST398) isolate has emerged worldwide. Although there have been reports of invasive disease in humans, MRSA ST398 colonization is much more common in livestock and demonstrates especially high prevalence rates in pigs and calves. The aim of this study was to compare the genome sequence of an ST398 MRSA isolate with other S. aureus genomes in order to identify genetic traits that may explain the success of this particular lineage. Therefore, we determined the whole genome sequence of S0385, an MRSA ST398 isolate from a human case of endocarditis. The entire genome sequence of S0385 demonstrated considerable accessory genome content differences relative to other S. aureus genomes. Several mobile genetic elements that confer antibiotic resistance were identified, including a novel composite of an type V (5C2&5) Staphylococcal Chromosome Cassette mec (SCCmec) with distinct joining (J) regions. The presence of multiple integrative conjugative elements combined with the absence of a type I restriction and modification system on one of the two nuSa islands, could enhance horizontal gene transfer in this strain. The ST398 MRSA isolate carries a unique pathogenicity island which encodes homologues of two excreted virulence factors; staphylococcal complement inhibitor (SCIN) and von Willebrand factor-binding protein (vWbp). However, several virulence factors such as enterotoxins and phage encoded toxins, including Panton-Valentine leukocidin (PVL), were not identified in this isolate. Until now MRSA ST398 isolates did not cause frequent invasive disease in humans, which may be due to the absence of several common virulence factors. However, the proposed enhanced ability of these isolates to acquire mobile elements may lead to the rapid acquisition of determinants which contribute to virulence in human infections.


H2-DMalpha(-/-) mice show the importance of major histocompatibility complex-bound peptide in cardiac allograft rejection.
The role played by antigenic peptides bound to major histocompatibility complex (MHC) molecules is evaluated with H2-DMalpha(-/)- mice. These mice have predominantly class II-associated invariant chain peptide (CLIP)-, not antigenic peptide-bound, MHC class II. H2-DMalpha(-/)- donor heart grafts survived three times longer than wild-type grafts and slightly longer than I-A(beta)(b)-(/)- grafts. Proliferative T cell response was absent, and cytolytic response was reduced against the H2-DMalpha(-/)- grafts in vivo. Residual cytolytic T cell and antibody responses against intact MHC class I lead to eventual rejection. Removal of both H2-DMalpha and beta2-microglobulin (beta2m) in cardiac grafts lead to greater (8-10 times) graft survival, whereas removal of beta2m alone did not have any effect. These results demonstrate the significance of peptide rather than just allogeneic MHC, in eliciting graft rejection.


Identification of small molecule inhibitors of pre-mRNA splicing.
Eukaryotic pre-mRNA splicing is an essential step in gene expression for all genes that contain introns. In contrast to transcription and translation, few well characterized chemical inhibitors are available with which to dissect the splicing process, particularly in cells. Therefore, the identification of specific small molecules that either inhibit or modify pre-mRNA splicing would be valuable for research and potentially also for therapeutic applications. We have screened a highly curated library of 71,504 drug-like small molecules using a high throughput in vitro splicing assay. This identified 10 new compounds that both inhibit pre-mRNA splicing in vitro and modify splicing of endogenous pre-mRNA in cells. One of these splicing modulators, DDD00107587 (termed "madrasin," i.e. 2-((7methoxy-4-methylquinazolin-2-yl)amino)-5,6-dimethylpyrimidin-4(3H)-one RNAsplicing inhibitor), was studied in more detail. Madrasin interferes with the early stages of spliceosome assembly and stalls spliceosome assembly at the A complex. Madrasin is cytotoxic at higher concentrations, although at lower concentrations it induces cell cycle arrest, promotes a specific reorganization of subnuclear protein localization, and modulates splicing of multiple pre-mRNAs in both HeLa and HEK293 cells.


[Determination of Fe, Al, Ca in silicon metal by XRF spectrometry].
Fe, Al, Ca in silicon metal were measured by XRF using powder pressed method to prepare the sample. The conditions of preparing the sample disc were discussed, and the strength of the sample disc, was solidified through the binder added. Interelement absorption and enhancement effects are corrected by using the experience coefficient method. The precision and accuracy of the XRF method are excellent as compared with classical chemical method.


Spatial and temporal predictions of moose winter distribution.
Herbivores are usually distributed unevenly across the landscape often because of variation in resource availability. We used zero-inflated generalised additive models (to account for data with a high number of zeros) that include georeferences to predict winter distribution of a large herbivore (moose Alces alces). Moose distribution was analysed in relation to forage availability and distance to neighbouring sites. Our results showed that the ability to explain moose distribution indexed by pellet count data at a local scale increased when spatial information (longitude and latitude) was added to the model compared to the model only including food availability. By using the relationship between moose and forage distribution, and the spatial information, we predicted patch choice by moose reasonably well in 2 out of 4 years. However, the distribution of moose was also influenced by weather conditions, as it was most clumped in the year with most snow. In conclusion, our study lends support for a non-linear approach using georeferences for a comprehensive understanding of herbivore distribution at a small scale. This result also indicates that the use of a certain patch by moose not only depends on the selected patch itself but is also influenced by the neighbouring patch and factors at a larger spatial scale, such as moose management influencing the density above moose home range level. The relatively high proportion of unexplained variation suggests that the use of a certain patch is also influenced by other factors such as topography, predation, competition, weather conditions, and wildlife management strategies.


Allgrove Syndrome: A Report of New Pathological Variants in the AAAS Gene.
To report 2 novel variants in the AAAS gene consistent with the diagnosis of Allgrove syndrome. A 12-year-old girl was referred to our clinic for progressive bilateral decrease in visual acuity. She was known for achalasia that had been surgically treated at a very early age. On examination, she was found to have dry eye disease secondary to lacrimal insufficiency. She also had anisocoria, light-near dissociation, and bilateral optic nerve atrophy. Neurological examination and brain magnetic resonance imaging were within normal limits. Genetic workup revealed compound heterozygosity for 2 novel variants in the AAAS gene, confirming the diagnosis of Allgrove syndrome. The patient was referred to endocrinology to screen for adrenocorticotropic hormone insufficiency. She was started on topical lubricating therapy that improved her symptoms. Allgrove syndrome is a rare genetic disease that is characterized by the triad of achalasia, alacrima, and adrenal insufficiency. Early diagnosis, confirmed with genetic testing, is essential to initiate an appropriate follow-up and prevent a life-threatening addisonian crisis. Report of novel mutations is important to further characterize this disease.


Saving Saba bank: policy implications of biodiversity studies.
Saba Bank has always been an area of special importance to the neighboring island of Saba in the Netherlands Antilles. Sabans traditionally fished on the Bank as far back as 1907, but increasing foreign fishing pressures on the Bank in the 1970s and 1980s forced many Saban fishermen out. Concerns were compounded by the suspicion that shipping was also damaging the benthic habitat of the bank. Fishery legislation, enacted in 1996, brought an end to unlicensed fishing and established Coast Guard enforcement on the Bank, but also led to protests from neighboring countries that previously fished on the Bank.Research was necessary to support the need for protection. Review of available research of Saba Bank and rapid biological assessments and fisheries surveys since 1996 emphasized the richness of Saba Bank's biodiversity and the need for protection of fisheries stocks. The national nature policy plan recognized this and encouraged further research to base conservation measures on.Recent biological surveys of corals, fishes, and algae presented in this collection of articles emphasized habitat heterogeneity and the relative richness of the marine flora and fauna. These assessments formed the basis for a management plan to protect Saba Bank's biodiversity and a draft proposal to the International Maritime Organization (IMO) seeking Particularly Sensitive Sea Area (PSSA) status for the Bank. The intention of the PSSA proposal is to protect the benthic habitat on Saba Bank from anchor damage. This paper serves to provide the context for the results of the recent biodiversity surveys of Saba Bank. It is hoped that this collection will serve as a knowledge baseline and engender further research in the area.


Reports of maternal socialization goals, emotion socialization behaviors, and child functioning in China and India.
A body of literature connects parental emotion socialization behaviors to child outcomes, though little research attention has been devoted to parents' culturally embedded socialization goals that influence their socialization behaviors in diverse samples. In the present study, we examined interrelations among maternal socialization goals, emotion socialization behaviors, and child functioning in families from 2 major Asian countries, China and India. A total of 305 6th and 7th grade children and their mothers across both countries participated. Mothers completed measures of their socialization goals, their responses to children's emotions, child behavior problems, and children completed a measure of emotion regulation (ER) at a single point in time. Factor analysis of the measure of parental responses to children's emotions yielded 2 factors (supportive and nonsupportive responses), with some items from the commonly used parent-report measure Coping with Children's Negative Emotions Scale (Fabes, Eisenberg, & Bernzweig, 1990), while others reflected culturally salient socialization approaches in Asia (i.e., child training, explanation). Using these data-driven supportive and nonsupportive response composites, mediation models were tested for the full sample. Reports of mothers' supportive responses and child ER sequentially mediated the relation between maternal relational socialization goals and child internalizing problems. Reports of child emotion dysregulation mediated the relation between maternal nonsupportive responses and child externalizing problems. Findings of this study highlight the relevance of culturally salient parental socialization goals and socialization behaviors in understanding child functioning in diverse cultural groups. (PsycINFO Database Record


"I'm not going to make a song and dance about it...".
Having been involved with the biomedical sciences and alternatives for 30 of the 50 years since Russell and Burch published The Principles of Humane Experimental Technique, I feel well placed to speak of the contributions made by FRAME over the last 40 years. FRAME has promoted the development and use of alternatives by presenting the "better science" arguments to scientists, promoting informed discussion, changing opinions and changing behaviours. FRAME has also contributed constructively to the political debate, and was instrumental in promoting legislation which incorporated the principles of the Three Rs. Times are changing, and the Three Rs are increasing being politicised: and FRAME is particularly well placed to ensure that good science and good welfare, rather than ideology, remain the basis for interest in and progress with the Three Rs.


A developmental fMRI study of reading and repetition reveals changes in phonological and visual mechanisms over age.
In this study of reading development, children (ages 7-10) and adults (ages 18-32) performed overt single-word reading and aural repetition tasks on high-frequency word stimuli during functional magnetic resonance imaging. Most regions showed similar activity across age groups. These widespread regions of similarity indicate that children and adults use largely overlapping mechanisms when processing high-frequency words. Significant task-related differences included greater activity in occipital cortex for the read task, and greater activity in temporal cortex for the repeat task; activity levels in these regions were similar for adults and children. However, age group differences were found in several posterior regions, including a set of regions implicated in adult reading: the left supramarginal gyrus, the left angular gyrus, and bilateral anterior extrastriate cortex. The angular and supramarginal gyrus regions, hypothesized to play a role in phonology, showed decreased activity in adults relative to children for high-frequency words. The extrastriate regions had significant activity for both the visual read task and auditory repeat task in children, but just for the read task in adults, showing significant task and age interactions. These results are consistent with decreasing reliance on phonological processing, and increasing tuning of visual mechanisms, with age.


Do infants show generalized imitation of gestures? II. The effects of skills training and multiple exemplar matching training.
The determinants of generalized imitation of manual gestures were investigated in 1- to 2-year-old infants. Eleven infants were first trained eight baseline matching relations; then, four novel gestures that the infants did not match in probe trials were selected as target behaviors. Next, in a generalized imitation test in which matching responses to baseline models were intermittently reinforced, but matching responses to target models were not eligible for reinforcement, the infants matched baseline models but not the majority of their target behaviors. To ensure their failure to match the target behaviors was not due to motor constraints, the infants were trained, in a multiple-baseline procedure, to produce the target responses under stimulus control that did not include an antecedent model of the target behavior. There was no evidence of generalized imitation in subsequent tests. When the infants were next trained to match each target behavior to criterion (tested in extinction) in a multiple-baseline-across-behaviors procedure, only 2 infants continued to match all their targets in subsequent tests; the remaining infants matched only some of them. Seven infants were next given mixed matching training with the target behaviors to criterion (tested in extinction); they subsequently matched these targets without reinforcement when interspersed with trials on which matching responses to baseline models were intermittently reinforced. In repeat tests, administered at 3-week intervals, these 7 children (and 2 that did not take part in mixed matching training) continued to match most of their target behaviors. The results support a trained matching account, but provide no evidence of generalized imitation, in 1- to 2-year-old infants.


Expression of C9orf72-related dipeptides impairs motor function in a vertebrate model.
Large expansions of hexanucleotide GGGGCC (G4C2) repeats (hundreds to thousands) in the first intron of the chromosome 9 open reading frame 72 (C9orf72) locus are the strongest known genetic factor associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Different hypotheses exist about the underlying disease mechanism including loss of function by haploinsufficiency, toxicity arising as a result of RNA or dipeptide repeats (DPRs). Five different DPRs are produced by repeat-associated non-ATG-initiated translation of the G4C2 repeats. Though earlier studies have indicated toxicity of the DPRs in worms, flies, primary cultured cells and cell lines, the effect of expressing DPRs of amyotrophic lateral sclerosis-relevant length has not been tested on motor behaviour in vertebrate models. In this study, by expressing constructs with alternate codons encoding different lengths of each DPR (40, 200 and 1000) in the vertebrate zebrafish model, the GR DPR was found to lead to the greatest developmental lethality and morphological defects, and GA, the least. However, expressing 1000 repeats of any DPR, including the 'non-toxic' GA DPR led to locomotor defects. Based on these observations, a transgenic line stably expressing 100 GR repeats was generated to allow specific regional and temporal expression of GR repeats in vivo. Expression of GR DPRs ubiquitously resulted in severe morphological defects and reduced swimming. However, when expressed specifically in motor neurons, the developmental defects were significantly reduced, but the swimming phenotype persisted, suggesting that GR DPRs have a toxic effect on motor neuron function. This was validated by the reduction in motor neuron length even in already formed motor neurons when GR was expressed in these. Hence, the expression of C9orf72-associated DPRs can cause significant motor deficits in vertebrates.