Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement

We have previously reported that an X-linked recessive form of chronic idiopathic intestinal pseudo-obstruction (CIIPX) maps to Xq28. To select candidate genes for the disease, we analyzed the expression in murine fetal brain and intestine of 56 genes from the critical region. We selected and sequenced seven genes and found that one affected male from a large CIIPX-affected kindred bears a 2-bp deletion in exon 2 of the FLNA gene that is present at the heterozygous state in the carrier females of the family. The frameshift mutation is located between two close methionines at the filamin N terminus and is predicted to produce a protein truncated shortly after the first predicted methionine. Loss-of-function FLNA mutations have been associated with X-linked dominant nodular ventricular heterotopia (PVNH), a central nervous system (CNS) migration defect that presents with seizures in females and lethality in males. Notably, the affected male bearing the FLNA deletion had signs of CNS involvement and potentially has PVNH. To understand how the severe frameshift mutation we found can explain the CIIPX phenotype and its X-linked recessive inheritance, we transiently expressed both the wild- type and mutant filamin in cell culture and found that filamin translation can start from either of the two initial methionines in these conditions. Therefore, translation of a normal shorter filamin can occur in vitro from the second methionine downstream of the 2-bp insertion we found. We confirmed this, demonstrating that the filamin protein is present in the patient's lymphoblastoid cell line that shows abnormal cytoskeletal actin organization compared with normal lymphoblasts. We conclude that the filamin N terminal region between the initial two methionines is crucial for proper enteric neuron development.     

Mirror mirror on the ward,who’s the most narcissistic of them all? Pathologic personality traits in health care

Background:

Stereotypes in medicine have become exaggerated for the purpose of workplace amusement. Our objective was to assess the levels of “dark triad” personality traits expressed by individuals working in different health care specialties in comparison with the general population.

Methods:

We conducted a prospective, cross-sectional study within multiple departments of a UK secondary care teaching hospital. A total of 248 health care professionals participated, and 159 members of the general population were recruited as a comparison group. We measured 3 personality traits — narcissism, Machiavellianism and psychopathy — through the validated self-reported personality questionnaires Narcissistic Personality Inventory (NPI), MACH-IV and the Levenson Self-Report Psychopathy Scale (LSRP), respectively.

Results:

Health care professionals scored significantly lower on narcissism, Machiavellianism and psychopathy (mean scores 12.0, 53.0 and 44.7, respectively) than the general population (p < 0.001). Nursing professionals exhibited a significantly higher level of secondary psychopathy than medical professionals (p = 0.04, mean LSRP score 20.3). Within the cohort of medical professionals, surgeons expressed significantly higher levels of narcissism (p = 0.03, mean NPI score 15.0).

Interpretation:

Health care professionals expressed low levels of dark triad personality traits. The suggestion that health care professionals are avaricious and untrustworthy may be refuted, even for surgeons.I was quietly admiring my astonishing good looks in the mirror of the operating theatre changing room when one of my anesthesiologist colleagues brazenly interrupted me: “Typical surgeon — you love yourselves so much we’ll need to have the mirrors removed in here if we are to get any work done!” I was somewhat bemused by the 2 obvious inaccuracies in this comment: first, that all surgeons love themselves and, second, that theatre workflow is ever dependent on the work ethos of the surgical team! I immediately went on the counteroffensive by replying, “Don’t worry, sudoku writers are on strike this week so we should be finished before lunch!”These lighthearted, tongue-in-cheek exchanges between medical professionals occur around the world every day and are based on popular stereotypes that have become exaggerated for the purpose of workplace amusement. One might imagine neanderthalic orthopedic surgeons instinctively reaching for a bigger hammer as the singular solution to any problem, grumpy radiologists growling at anyone who dares disturb their dark sanctuary and dour internists glacially grinding their way through a ward round, which necessitates a packed lunch, comfortable walking shoes and a hospital map.Many stereotypes have filtered into the public domain, where emphasis on negative traits can be misleading for the general public. The callous notion that doctors are self-centred, avaricious and untrustworthy is currently being bandied around the media.^1,2 There is a real danger of these negative stereotypes eroding the high level of regard in which the profession is held. Perhaps the most undesirable personality characteristics are those that form the “dark triad”: a trio of Machiavellianism, narcissism and psychopathy.³Those expressing Machiavellian traits are deceptive, self-interested and succeed through the exploitation of others.^4–6 Narcissism is defined as a “normal” personality trait at low levels and is characterized by the expression of pride, egotism and vanity.^7,8 Psychopathy manifests as antisocial behaviour expressing callousness, remorselessness and selfishness, with little empathy and a high level of impulsivity.^9,10 It has been proposed that 2 variants of psychopathy exist: primary and secondary. Primary psychopathy is believed to be a genetic predisposition to certain behavioural patterns, which include cool, calm, meticulous forward planning and emotional dissociation. Secondary psychopathy, however, is an adaptation to environmental factors and involves impulsivity and emotional instability, which can place others at risk.¹¹It is hypothesized that some of these dark personality traits are present within the health care profession and, more specifically, within certain disciplines. It is not implausible for one to conceive that the self-assured surgeon could display evidence of vanity or that the irrational nurse might exhibit psychopathic tendencies. However, scientific evidence is lacking to support or quantify the existence of such personality traits in the health care profession.The aim of this study was to assess levels of dark triad personality traits among individuals working in health care in comparison with the general population.     

Synapsin phosphorylation by SRC tyrosine kinase enhances SRC activity in synaptic vesicles

Synapsins are synaptic vesicle-associated phosphoproteins implicated in the regulation of neurotransmitter release. Synapsin I is the major binding protein for the SH3 domain of the kinase c-Src in synaptic vesicles. Its binding leads to stimulation of synaptic vesicle-associated c-Src activity. We investigated the mechanism and role of Src activation by synapsins on synaptic vesicles. We found that synapsin is tyrosine phosphorylated by c-Src in vitro and on intact synaptic vesicles independently of its phosphorylation state on serine. Mass spectrometry revealed a single major phosphorylation site at Tyr(301), which is highly conserved in all synapsin isoforms and orthologues. Synapsin tyrosine phosphorylation triggered its binding to the SH2 domains of Src or Fyn. However, synapsin selectively activated and was phosphorylated by Src, consistent with the specific enrichment of c-Src in synaptic vesicles over Fyn or n-Src. The activity of Src on synaptic vesicles was controlled by the amount of vesicle-associated synapsin, which is in turn dependent on synapsin serine phosphorylation. Synaptic vesicles depleted of synapsin in vitro or derived from synapsin null mice exhibited greatly reduced Src activity and tyrosine phosphorylation of other synaptic vesicle proteins. Disruption of the Src-synapsin interaction by internalization of either the Src SH3 or SH2 domains into synaptosomes decreased synapsin tyrosine phosphorylation and concomitantly increased neurotransmitter release in response to Ca(2+)-ionophores. We conclude that synapsin is an endogenous substrate and activator of synaptic vesicle-associated c-Src and that regulation of Src activity on synaptic vesicles participates in the regulation of neurotransmitter release by synapsin.     

Effect of CO2 and phosphate deprivation on the control of nitrate, nitrite and ammonium metabolism in Chlorella

Chlorella vulgaris Beijerinck, strain 211/12, uses nitrate, nitrite and ammonium at pH 8.2 but not at pH 6.4 when kept under conditions of CO₂-deprivation, as observed in cell suspensions aerated with CO₂-free air during a 20–30. h period Most of the nitrate absorbed at pH 8.2, however, was not assimilated but was released into the external medium as nitrite and ammonium. Cells of Chlorella previously grown in phosphate-limited continuous cultures were unable to absorb nitrate, nitrite or ammonium under conditions of phosphate starvation at either pH 6.4 or 8.2 in cell suspensions flushed with air containing 5% CO₂, However, in cell suspensions flushed with CO₂-free air, the capacity of the alga to absorb and reduce nitrate and to excrete nitrite and ammonium at pH 8.2 was restored.
It is hypothesized that in Chlorella the metabolism of nitrate, nitrite and ammonium is influenced by the availability of other nutrients and controlled by the cell's carbon status at the level of ion entry into the cell. With respect to nitrate this carbon-dependent control is distinct and works independently of that triggered by the cell's nitrogen status.     

Solid phase synthesis of cyclic peptides: model studies involving i−(i+4) side chain-to-side chain cyclisation

Conditions for the synthesis of i−(i+4) side chain-to-side chain head-to-tail Lys→Glu and Glu→Lys linked cyclic peptides related to hypoglycaemic analogues of human growth hormone hGH [6–13] have been examined. The success of the cyclisation reaction with the corresponding resin-bound, partially protected linear peptides was found to be both reagent as well as sequence dependent, with competing inter-chain oligomerisation predominating in some cases. The results also indicated that protection with the bulky Fmoc group of the amino acid residues immediately adjacent to the side chain-deprotected Lys and Glu residues, which participate in the cyclisation reaction, enhanced the rate of lactam formation. © 1998 European Peptide Society and John Wiley & Sons, Ltd.     

Monitoring of tropical freshwater fish resources for sustainable use

Tropical freshwater ecosystems are some of the world's most biodiverse and productive systems where determining what sustainable exploitation of inland fisheries looks like is particularly challenging. One of the greatest obstacles to sustainable management is collecting and using quality data on fish production and yield. The biodiversity and hydro-ecology of these systems often under open-access governance, add to the complexity of managing them. This paper describes an integrated citizen-science, earth observation, environmental DNA and independent survey approach to collecting fish and fisheries data, using the Cambodian Mekong as a case study.     

An Integrated Approach Based on Multiplexed Protein Array and iTRAQ Labeling for In-Depth Identification of Pathways Associated to IVF Outcome

The emergence of high-throughput protein quantification methodologies has enabled the comprehensive characterization by longitudinal and cross-sectional studies of biological fluids under physiological and pathological conditions. In particular, the simultaneous investigation of cytokines and growth factors signaling pathways and their associated downstream effectors by integrated multiplexed approaches offers a powerful strategy to gain insights into biological networks and processes in living systems. A growing body of research indicates that bioactive molecules of human reproductive fluids, including human follicular fluid (hFF), may affect oocyte quality, fertilization and embryo development, thus potentially influencing the physiopathology of pregnancy-related conditions.In this work, an iTRAQ labeling strategy has been complemented with a multiplexed protein array approach to analyze hFFs with the aim to investigate biological processes and pathways related to in vitro fertilization (IVF) outcome. The iTRAQ labeling strategy lead to the quantification of 89 proteins, 30 of which were differentially expressed in hFFs with successful compared to unsuccessful IVF outcome. The targeted study, based on multiplexed antibody protein arrays, allowed the simultaneous quantification of 27 low abundance proteins, including growth factors, chemokines and cytokines endowed with pro- and anti-inflammatory activity. A significant number of differentially regulated proteins were involved in biological functions related to blood coagulation, acute phase response signaling and complement system. Overall, the present results provide an integrated overview of protein changes in hFFs associated to IVF outcome, thus improving current knowledge in reproductive medicine and fertility research.     

Contrasting life-history traits of two sympatric smooth-hound species: implication for vulnerability

In this study, life-history traits (maximum and average size, size at maturity and fecundity) of two congeneric smooth-hounds, Mustelus mustelus and Mustelus punctulatus, which share a geographical distribution and experience a similar fishing exploitation, were estimated and compared between species. The results indicated a lower maximum and average size, a lower size at maturity and a higher fecundity in M. punctulatus compared with those in M. mustelus. Considering that these two species co-occur in the same areas and are caught by the same fishing gears, the results indicate a higher vulnerability to exploitation of M. mustelus compared with that of M. punctulatus.     

Maternal influence on the development of nut‐cracking skills in the chimpanzees of the Taï forest,Côte d'Ivoire (Pan troglodytes verus)

Chimpanzees’ (Pan troglodytes) nut‐cracking behavior represents one of the most complex forms of tool‐use known among nonhuman animals. Given the close phylogenetic relationship between these apes and humans, investigating how such complex behavior develops in immatures can reveal the evolutionary roots of the cognitive processes that enabled the evolution of outstanding technological skills in our lineage. In this study, we investigated whether maternal behavior directly enhanced nut‐cracking skills in immature individuals. We analyzed the behavior of 11 immatures and their mothers (N = 8) during nut‐cracking activity, spanning over three consecutive nut‐cracking seasons in the Taï National Park, Côte d'Ivoire. We used generalized linear mixed models to (a) obtain values of maternal scaffolding (defined as provision of learning opportunities) and active nut‐sharing behavior of each mother according to the age of their offspring, and their average nut‐cracking efficiency; (b) to test whether these variables enhanced immatures’ nut‐cracking skills; and (c) to test whether immatures’ features (age, sex, and begging behavior) influenced maternal behavior as observed in our videos. Although the predicted values of maternal scaffolding and active nut‐sharing did not obviously affect immatures’ skills, they were positively influenced by the average maternal efficiency and by sharing hammers with their mothers. In addition, our observations showed that mothers were more likely to share nuts with their sons than with their daughters, and the more their offspring begged. Concurrently, male immatures were also found to beg more often than females. Our results add evidence on the ontogenetic pathway leading to the full acquisition of nut‐cracking in wild chimpanzees and on the effect that maternal behavior can have in promoting the acquisition of this complex tool‐use behavior. Moreover, our study strengthens the importance of naturalistic observations to understand complex skill acquisition. Finally, we suggest future avenues for investigating the maternal influence on learning.