Characteristics of Attempted Suicide by Patients with Schizophrenia Compared with Those with Mood Disorders: A Case-Controlled Study in Northern Japan

Recent reports suggest a lifetime suicide risk for schizophrenia patients of approximately 5%. This figure is significantly higher than the general population suicide risk consequently, detection of those at risk is clinically important. This study was undertaken to define the characteristics of suicide attempts by schizophrenia patients compared with attempts by patients with mood disorders. All patients were diagnosed using the ICD-10 criteria. The study population comprised 65 patients with F2 disorders (schizophrenia, schizotypal and delusional disorders), i.e., “the F2 group”, and 94 patients with F3 disorders (mood disorders), i.e., “the F3 group”, who presented in the clinical setting of consultation-liaison psychiatry. The F2 group had a significantly younger mean age and significantly higher ratios of ‘past/present psychiatric treatment’ and ‘more than 3 months interruption of psychiatric treatment’. In contrast, the ratios of ‘physical disorder comorbidity’, ‘alcohol intake at suicide attempt’ and ‘suicide note left behind’ were significantly higher in the F3 group. The F2 group attempted suicide by significantly more serious methods. Furthermore, ‘hallucination-delusion’ was the most prevalent motive in the F2 group and was the only factor that showed a significant association with the seriousness of the method of suicide attempt (OR = 3.36, 95% CI: 1.05–11.33).     

Beyond a Dichotomous View of the Concepts of ‘Sex’ and ‘Gender’ Focus Group Discussions among Gender Researchers at a Medical Faculty

Introduction

The concepts of ‘sex’ and ‘gender’ are both of vital importance in medicine and health sciences. However, the meaning of these concepts has seldom been discussed in the medical literature. The aim of this study was to explore what the concepts of ‘sex’ and ‘gender’ meant for gender researchers based in a medical faculty.

Methods

Sixteen researchers took part in focus group discussions. The analysis was performed in several steps. The participating researchers read the text and discussed ideas for analysis in national and international workshops. The data were analysed using qualitative content analysis. The authors performed independent preliminary analyses, which were further developed and intensively discussed between the authors.

Results

The analysis of meanings of the concepts of ‘sex’ and ‘gender’ for gender researchers based in a medical faculty resulted in three categories; “Sex as more than biology”, with the subcategories ‘sex’ is not simply biological, ‘sex’ as classification, and ‘sex’ as fluid and changeable; ”Gender as a multiplicity of power-related constructions”, with the subcategories: ‘gender’ as constructions, ‘gender’ power dimensions, and ‘gender’ as doing femininities and masculinities; “Sex and gender as interwoven”, with the subcategories: ‘sex’ and ‘gender’ as inseparable and embodying ‘sex’ and ‘gender’.

Conclusions

Gender researchers within medicine pointed out the importance of looking beyond a dichotomous view of the concepts of ‘sex’ and ‘gender’. The perception of the concepts was that ‘sex’ and ‘gender’ were intertwined. Further research is needed to explore how ‘sex’ and ‘gender’ interact.     

Body composition adaptations to lower-body plyometric training: a systematic review and meta-analysis

The aim of this meta-analysis was to explore the effects of plyometric jump training (PJT) on body composition parameters among males. Relevant articles were searched in the electronic databases PubMed, MEDLINE, WOS, and SCOPUS, using the key words “ballistic”, “complex”, “explosive”, “force-velocity”, “plyometric”, “stretch-shortening cycle”, “jump”, “training”, and “body composition”. We included randomized controlled trials (RCTs) that investigating the effects of PJT in healthy male’s body composition (e.g., muscle mass; body fat), irrespective of age. From database searching 21 RCTs were included (separate experimental groups = 28; pooled number of participants = 594). Compared to control, PJT produced significant increases in total leg muscle volume (small ES = 0.55, p = 0.009), thigh muscle volume (small ES = 0.38, p = 0.043), thigh girth (large ES = 1.78, p = 0.011), calf girth (large ES = 1.89, p = 0.022), and muscle pennation angle (small ES = 0.53, p = 0.040). However, we did not find significant difference between PJT and control for muscle cross-sectional area, body fat, and skinfold thickness. Heterogeneity remained low-to-moderate for most analyses, and using the Egger’s test publication bias was not found in any of the analyses (p = 0.300–0.900). No injuries were reported among the included studies. PJT seems to be an effective and safe mode of exercise for increasing leg muscle volume, thigh muscle volume, thigh and calf girth, and muscle pennation angle. Therefore, PJT may be effective to improve muscle size and architecture, with potential implications in several clinical and sport-related contexts.     

Predictive Habitat Modelling as a Tool to Assess the Change in Distribution and Extent of an OSPAR Priority Habitat under an Increased Ocean Temperature Scenario: Consequences for Marine Protected Area Networks and Management

The aims of this study were to determine the extent and distribution of an OSPAR priority habitat under current baseline ocean temperatures; to illustrate the prospect for habitat loss under a changing ocean temperature scenario; and to demonstrate the potential application of predictive habitat mapping in “future-proofing” conservation and biodiversity management.Maxent modelling and GIS environmental envelope analysis of the biogenic bed forming species, Modiolus modiolus was carried out. The Maxent model was tested and validated using 75%/25% training/test occurrence records and validated against two sampling biases (the whole study area and a 20km buffer). The model was compared to the envelope analysis and the area under the receiver operating characteristic curve (Area Under the curve; AUC) was evaluated.The performance of the Maxent model was rated as ‘good’ to ‘excellent’ on all replicated runs and low variation in the runs was recorded from the AUC values. The extent of “most suitable”, “less suitable” and “unsuitable” habitat was calculated for the baseline year (2009) and the projected increased ocean temperature scenarios (2030, 2050, 2080 and 2100). A loss of 100% of “most suitable” habitat was reported by 2080.Maintaining a suitable level of protection of marine habitats/species of conservation importance may require management of the decline and migration rather than maintenance of present extent. Methods applied in this study provide the initial application of a plausible “conservation management tool”.     

Osteology of Pseudochampsa ischigualastensis gen. et comb. nov. (Archosauriformes: Proterochampsidae) from the Early Late Triassic Ischigualasto Formation of Northwestern Argentina

Proterochampsids are crocodile-like, probably semi-aquatic, quadrupedal archosauriforms characterized by an elongated and dorsoventrally low skull. The group is endemic from the Middle-Late Triassic of South America. The most recently erected proterochampsid species is “Chanaresuchus ischigualastensis”, based on a single, fairly complete skeleton from the early Late Triassic Ischigualasto Formation of northwestern Argentina. We describe here in detail the non-braincase cranial and postcranial anatomy of this species and revisit its taxonomy and phylogenetic relationships. The phylogenetic analysis recovered ‘Chanaresuchus ischigualastensis’ as part of a trichotomy together with Gualosuchus reigi and Chanaresuchus bonapartei. Accordingly, “Chanaresuchus ischigualastensis” can be potentially more closely related to Gualosuchus reigi, or even Rhadinosuchus gracilis, than to Chanaresuchus bonapartei. In addition, after discussing previously claimed synapomorphies of Chanaresuchus, we could not find unambiguous support for the monophyly of the genus. As a result, we propose here the erection of the new genus Pseudochampsa for ‘Chanaresuchus ischigualastensis’, which results in the new combination Pseudochampsa ischigualastensis. The information provided here about the anatomy and taxonomy of Pseudochampsa ischiguaslastensis will be useful for future quantitative analyses focused on the biogeography and macroevolutionary history of proterochampsids.     

Do Chinese Readers Follow the National Standard Rules for Word Segmentation during Reading?

We conducted a preliminary study to examine whether Chinese readers’ spontaneous word segmentation processing is consistent with the national standard rules of word segmentation based on the Contemporary Chinese language word segmentation specification for information processing (CCLWSSIP). Participants were asked to segment Chinese sentences into individual words according to their prior knowledge of words. The results showed that Chinese readers did not follow the segmentation rules of the CCLWSSIP, and their word segmentation processing was influenced by the syntactic categories of consecutive words. In many cases, the participants did not consider the auxiliary words, adverbs, adjectives, nouns, verbs, numerals and quantifiers as single word units. Generally, Chinese readers tended to combine function words with content words to form single word units, indicating they were inclined to chunk single words into large information units during word segmentation. Additionally, the “overextension of monosyllable words” hypothesis was tested and it might need to be corrected to some degree, implying that word length have an implicit influence on Chinese readers’ segmentation processing. Implications of these results for models of word recognition and eye movement control are discussed.     

Characteristics of the Jejunal Microbiota in 35-Day-Old Saba and Landrace Piglets

The balanced microbiological system is a significant hallmark of piglet health. One of the crucial factors affecting intestinal microbiota is the host’s genetics. This study explored the difference in the diversity of jejunal microbiota between Saba (SB) and Landrace (LA) piglets. Nine Saba and nine Landrace piglets were fed with sow’s milk until day 35. Jejunal contents were harvested for 16S rRNA sequencing. The birth weight, body weight, and average daily gain of Saba piglets were lower than those of Landrace piglets (p < 0.01). Firmicutes were the main phylum in Saba and Landrace piglets, and the Saba piglets had a higher (p < 0.05) abundance of Bacteroidetes compared with Landrace piglets. The two most abundant genera were Lactobacilli and Clostridium XI in the jejunum of Landrace and Saba piglets. Compared with Landrace piglets, the Saba piglets had significantly lower (p < 0.05) abundance of Veillonella, Streptococcus, and Saccharibacteria genera incertae sedis. The functional prediction showed that “d-glutamine and d-glutamate metabolism” and “one carbon pool by folate” pathways were enriched in Saba piglets, while “limonene and pinene degradation”, “tryptophan metabolism”, and “sulfur relay system” pathways were enriched in Landrace piglets. In summary, the growth performance was higher for Landrace piglets compared with Saba piglets due to their genetic characteristics. The rich diversity and fewer infection-associated taxa were observed in Saba piglets, partially accounting for their higher adaptability to environmental perturbations than Landrace piglets. Furthermore, different pig breeds may regulate their health through different metabolic pathways.Key words: Saba piglets, Landrace piglets, jejunal content, the 16S rRNA gene, diversity     

Exercise Tolerance Can Be Enhanced through a Change in Work Rate within the Severe Intensity Domain: Work above Critical Power Is Not Constant

Introduction

The characterization of the hyperbolic power-time (P-t _lim) relationship using a two-parameter model implies that exercise tolerance above the asymptote (Critical Power; CP), i.e. within the severe intensity domain, is determined by the curvature (W’) of the relationship.

Purposes

The purposes of this study were (1) to test whether the amount of work above CP (W>CP) remains constant for varied work rate experiments of high volatility change and (2) to ascertain whether W’ determines exercise tolerance within the severe intensity domain.

Methods

Following estimation of CP (208 ± 19 W) and W’ (21.4 ± 4.2 kJ), 14 male participants (age: 26 ± 3; peak V˙O2: 3708 ± 389 ml.min^-1) performed two experimental trials where the work rate was initially set to exhaust 70% of W’ in 3 (‘THREE’) or 10 minutes (‘TEN’) before being subsequently dropped to CP plus 10 W.

Results

W>CP for TEN (104 ± 22% W’) and W’ were not significantly different (P>0.05) but lower than W>CP for THREE (119 ± 17% W’, P<0.05). For both THREE (r = 0.71, P<0.01) and TEN (r = 0.64, P<0.01), a significant bivariate correlation was found between W’ and t _lim.

Conclusion

W>CP and t _lim can be greater than predicted by the P-t _lim relationship when a decrement in the work rate of high-volatility is applied. Exercise tolerance can be enhanced through a change in work rate within the severe intensity domain. W>CP is not constant.     

Validation of the Early Warning and Response System (EWARS) for dengue outbreaks: Evidence from the national vector control program in Mexico

BackgroundDuring 2017, twenty health districts (locations) implemented a dengue outbreak Early Warning and Response System (EWARS) in Mexico, which processes epidemiological, meteorological and entomological alarm indicators to predict dengue outbreaks and triggers early response activities.Out of the 20 priority districts where more than one fifth of all national disease transmission in Mexico occur, eleven districts were purposely selected and analyzed. Nine districts presented outbreak alarms by EWARS but without subsequent outbreaks (“non-outbreak districts”) and two presented alarms with subsequent dengue outbreaks (“outbreak districts”). This evaluation study assesses and compares the impact of alarm-informed response activities and the consequences of failing a timely and adequate response across the outbreak groups.MethodsFive indicators of dengue outbreak response (larval control, entomological studies with water container interventions, focal spraying and indoor residual spraying) were quantitatively analyzed across two groups (”outbreak districts” and “non-outbreak districts”). However, for quality control purposes, only qualitative concluding remarks were derived from the fifth response indicator (fogging).ResultsThe average coverage of vector control responses was significantly higher in non-outbreak districts and across all four indicators. In the “outbreak districts” the response activities started late and were of much lower intensity compared to “non-outbreak districts”. Vector control teams at districts-level demonstrated diverse levels of compliance with local guidelines for ‘initial’, ‘early’ and ‘late’ responses to outbreak alarms, which could potentially explain the different outcomes observed following the outbreak alarms.ConclusionFailing timely and adequate response of alarm signals generated by EWARS showed to negatively impact the disease outbreak control process. On the other hand, districts with adequate and timely response guided by alarm signals demonstrated successful records of outbreak prevention. This study presents important operational scenarios when failing or successding EWARS but warrants investigating the effectiveness and cost-effectiveness of EWARS using a more robust designs.     

Morals Matter in Economic Games

Contrary to predictions from Expected Utility Theory and Game Theory, when making economic decisions in interpersonal situations, people take the interest of others into account and express various forms of solidarity, even in one-shot interactions with anonymous strangers. Research in other-regarding behavior is dominated by behavioral economical and evolutionary biological approaches. Psychological theory building, which addresses mental processes underlying other-regarding behavior, is rare. Based on Relational Models Theory (RMT, [1]) and Relationship Regulation Theory (RRT, [2]) it is proposed that moral motives influence individuals’ decision behavior in interpersonal situations via conscious and unconscious (automatic) processes. To test our propositions we developed the ‘Dyadic Solidarity Game’ and its solitary equivalent, the ‘Self-Insurance Game’. Four experiments, in which the moral motives “Unity” and “Proportionality” were manipulated, support the propositions made. First, it was shown that consciously activated moral motives (via framing of the overall goal of the experiment) and unconsciously activated moral motives (via subliminal priming) influence other-regarding behavior. Second, this influence was only found in interpersonal, not in solitary situations. Third, by combining the analyses of the two experimental games the extent to which participants apply the Golden Rule (“treat others how you wish to be treated”) could be established. Individuals with a “Unity” motive treated others like themselves, whereas individuals with a “Proportionality” motive gave others less then they gave themselves. The four experiments not only support the assumption that morals matter in economic games, they also deliver new insights in how morals matter in economic decision making.     

Neural signatures of syntactic variation in speech planning

Planning to speak is a challenge for the brain, and the challenge varies between and within languages. Yet, little is known about how neural processes react to these variable challenges beyond the planning of individual words. Here, we examine how fundamental differences in syntax shape the time course of sentence planning. Most languages treat alike (i.e., align with each other) the 2 uses of a word like “gardener” in “the gardener crouched” and in “the gardener planted trees.” A minority keeps these formally distinct by adding special marking in 1 case, and some languages display both aligned and nonaligned expressions. Exploiting such a contrast in Hindi, we used electroencephalography (EEG) and eye tracking to suggest that this difference is associated with distinct patterns of neural processing and gaze behavior during early planning stages, preceding phonological word form preparation. Planning sentences with aligned expressions induces larger synchronization in the theta frequency band, suggesting higher working memory engagement, and more visual attention to agents than planning nonaligned sentences, suggesting delayed commitment to the relational details of the event. Furthermore, plain, unmarked expressions are associated with larger desynchronization in the alpha band than expressions with special markers, suggesting more engagement in information processing to keep overlapping structures distinct during planning. Our findings contrast with the observation that the form of aligned expressions is simpler, and they suggest that the global preference for alignment is driven not by its neurophysiological effect on sentence planning but by other sources, possibly by aspects of production flexibility and fluency or by sentence comprehension. This challenges current theories on how production and comprehension may affect the evolution and distribution of syntactic variants in the world’s languages.

Little is known about the neural processes involved in planning to speak. This study uses eye-tracking and EEG to show that speakers prepare sentence structures in different ways and rely on alpha and theta oscillations differently when planning sentences with and without agent case marking, challenging theories on how production and comprehension affect language evolution.     

A Moist Crevice for Word Aversion: In Semantics Not Sounds

Why do people self-report an aversion to words like “moist”? The present studies represent an initial scientific exploration into the phenomenon of word aversion by investigating its prevalence and cause. Results of five experiments indicate that about 10–20% of the population is averse to the word “moist.” This population often speculates that phonological properties of the word are the cause of their displeasure. However, data from the current studies point to semantic features of the word–namely, associations with disgusting bodily functions–as a more prominent source of peoples’ unpleasant experience. “Moist,” for averse participants, was notable for its valence and personal use, rather than imagery or arousal–a finding that was confirmed by an experiment designed to induce an aversion to the word. Analyses of individual difference measures suggest that word aversion is more prevalent among younger, more educated, and more neurotic people, and is more commonly reported by females than males.     

Methodological Deficits in Diagnostic Research Using ‘-Omics’ Technologies: Evaluation of the QUADOMICS Tool and Quality of Recently Published Studies

Background

QUADOMICS is an adaptation of QUADAS (a quality assessment tool for use in systematic reviews of diagnostic accuracy studies), which takes into account the particular challenges presented by ‘-omics’ based technologies. Our primary objective was to evaluate the applicability and consistency of QUADOMICS. Subsequently we evaluated and describe the methodological quality of a sample of recently published studies using the tool.

Methodology/Principal Findings

45‘-omics’- based diagnostic studies were identified by systematic search of Pubmed using suitable MeSH terms (“Genomics”, “Sensitivity and specificity”, “Diagnosis”). Three investigators independently assessed the quality of the articles using QUADOMICS and met to compare observations and generate a consensus. Consistency and applicability was assessed by comparing each reviewer''s original rating with the consensus. Methodological quality was described using the consensus rating. Agreement was above 80% for all three reviewers. Four items presented difficulties with application, mostly due to the lack of a clearly defined gold standard. Methodological quality of our sample was poor; studies met roughly half of the applied criteria (mean ± sd, 54.7±18.4%). Few studies were carried out in a population that mirrored the clinical situation in which the test would be used in practice, (6, 13.3%); none described patient recruitment sufficiently; and less than half described clinical and physiological factors that might influence the biomarker profile (20, 44.4%).

Conclusions

The QUADOMICS tool can consistently be applied to diagnostic ‘-omics’ studies presently published in biomedical journals. A substantial proportion of reports in this research field fail to address design issues that are fundamental to make inferences relevant for patient care.     

Differential Responses of CO2 Assimilation,Carbohydrate Allocation and Gene Expression to NaCl Stress in Perennial Ryegrass with Different Salt Tolerance

Little is known about the effects of NaCl stress on perennial ryegrass (Lolium perenne L.) photosynthesis and carbohydrate flux. The objective of this study was to understand the carbohydrate metabolism and identify the gene expression affected by salinity stress. Seventy-four days old seedlings of two perennial ryegrass accessions (salt-sensitive ‘PI 538976’ and salt-tolerant ‘Overdrive’) were subjected to three levels of salinity stress for 5 days. Turf quality in all tissues (leaves, stems and roots) of both grass accessions negatively and significantly correlated with GFS (Glu+Fru+Suc) content, except for ‘Overdrive’ stems. Relative growth rate (RGR) in leaves negatively and significantly correlated with GFS content in ‘Overdrive’ (P<0.01) and ‘PI 538976’ (P<0.05) under salt stress. ‘Overdrive’ had higher CO₂ assimilation and F_v/F_m than ‘PI 538976’. Intercellular CO₂ concentration, however, was higher in ‘PI 538976’ treated with 400 mM NaCl relative to that with 200 mM NaCl. GFS content negatively and significantly correlated with RGR in ‘Overdrive’ and ‘PI 538976’ leaves and in ‘PI 538976’ stems and roots under salt stress. In leaves, carbohydrate allocation negatively and significantly correlated with RGR (r² = 0.83, P<0.01) and turf quality (r² = 0.88, P<0.01) in salt-tolerant ‘Overdrive’, however, the opposite trend for salt-sensitive ‘PI 538976’ (r² = 0.71, P<0.05 for RGR; r² = 0.62, P>0.05 for turf quality). A greater up-regulation in the expression of SPS, SS, SI, 6-SFT gene was observed in ‘Overdrive’ than ‘PI 538976’. A higher level of SPS and SS expression in leaves was found in ‘PI 538976’ relative to ‘Overdrive’. Accumulation of hexoses in roots, stems and leaves can induce a feedback repression to photosynthesis in salt-stressed perennial ryegrass and the salt tolerance may be changed with the carbohydrate allocation in leaves and stems.     

Local hopping mobile DNA implicated in pseudogene formation and reductive evolution in an obligate cyanobacteria-plant symbiosis

Background

Insertion sequences (ISs) are approximately 1 kbp long “jumping” genes found in prokaryotes. ISs encode the protein Transposase, which facilitates the excision and reinsertion of ISs in genomes, making these sequences a type of class I (“cut-and-paste”) Mobile Genetic Elements. ISs are proposed to be involved in the reductive evolution of symbiotic prokaryotes. Our previous sequencing of the genome of the cyanobacterium ‘Nostoc azollae’ 0708, living in a tight perpetual symbiotic association with a plant (the water fern Azolla), revealed the presence of an eroding genome, with a high number of insertion sequences (ISs) together with an unprecedented large proportion of pseudogenes. To investigate the role of ISs in the reductive evolution of ‘Nostoc azollae’ 0708, and potentially in the formation of pseudogenes, a bioinformatic investigation of the IS identities and positions in 47 cyanobacterial genomes was conducted. To widen the scope, the IS contents were analysed qualitatively and quantitatively in 20 other genomes representing both free-living and symbiotic bacteria.

Results

Insertion Sequences were not randomly distributed in the bacterial genomes and were found to transpose short distances from their original location (“local hopping”) and pseudogenes were enriched in the vicinity of IS elements. In general, symbiotic organisms showed higher densities of IS elements and pseudogenes than non-symbiotic bacteria. A total of 1108 distinct repeated sequences over 500 bp were identified in the 67 genomes investigated. In the genome of ‘Nostoc azollae’ 0708, IS elements were apparent at 970 locations (14.3%), with 428 being full-length. Morphologically complex cyanobacteria with large genomes showed higher frequencies of IS elements, irrespective of life style.

Conclusions

The apparent co-location of IS elements and pseudogenes found in prokaryotic genomes implies earlier IS transpositions into genes. As transpositions tend to be local rather than genome wide this likely explains the proximity between IS elements and pseudogenes. These findings suggest that ISs facilitate the reductive evolution in for instance in the symbiotic cyanobacterium ‘Nostoc azollae’ 0708 and in other obligate prokaryotic symbionts.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1386-7) contains supplementary material, which is available to authorized users.     

'Asking the Right Question'. A Comparison of Two Approaches to Gathering Data on 'Herbals' Use in Survey Based Studies

Background

Over the last decade academic interest in the prevalence and nature of herbal medicines use by pregnant women has increased significantly. Such data are usually collected by means of an administered questionnaire survey, however a key methodological limitation using this approach is the need to clearly define the scope of ‘herbals’ to be investigated. The majority of published studies in this area neither define ‘herbals’ nor provide a detailed checklist naming specific ‘herbals’ and CAM modalities, which limits inter-study comparison, generalisability and the potential for meta-analyses. The aim of this study was to compare the self-reported use of herbs, herbal medicines and herbal products using two different approaches implemented in succession.

Methods

Cross-sectional questionnaire surveys of women attending for their mid-trimester scan or attending the postnatal unit following live birth at the Royal Aberdeen Maternity Hospital, North-East Scotland. The questionnaire utilised two approaches to collect data on ‘herbals’ use, a single closed yes/no answer to the question “have you used herbs, herbal medicines and herbal products in the last three months”; and a request to tick which of a list of 40 ‘herbals’ they had used in the same time period.

Results

A total of 889 responses were obtained of which 4.3% (38) answered ‘yes’ to herbal use via the closed question. However, using the checklist 39% (350) of respondents reported the use of one or more specific ‘herbals’ (p<0.0001). The 312 respondents who reported ‘no’ to ‘herbals’ use via the closed question but “yes” via the checklist consumed a total of 20 different ‘herbals’ (median 1, interquartile range 1–2, range 1–6).

Conclusions

This study demonstrates that the use of a single closed question asking about the use of ‘herbals’, as frequently reported in published studies, may not yield valid data resulting in a gross underestimation of actual use.     

Molecular Mechanisms,Thermodynamics, and Dissociation Kinetics of Knob-Hole Interactions in Fibrin

Polymerization of fibrin, the primary structural protein of blood clots and thrombi, occurs through binding of knobs ‘A’ and ‘B’ in the central nodule of fibrin monomer to complementary holes ‘a’ and ‘b’ in the γ- and β-nodules, respectively, of another monomer. We characterized the A:a and B:b knob-hole interactions under varying solution conditions using molecular dynamics simulations of the structural models of fibrin(ogen) fragment D complexed with synthetic peptides GPRP (knob ‘A’ mimetic) and GHRP (knob ‘B’ mimetic). The strength of A:a and B:b knob-hole complexes was roughly equal, decreasing with pulling force; however, the dissociation kinetics were sensitive to variations in acidity (pH 5–7) and temperature (T = 25–37 °C). There were similar structural changes in holes ‘a’ and ‘b’ during forced dissociation of the knob-hole complexes: elongation of loop I, stretching of the interior region, and translocation of the moveable flap. The disruption of the knob-hole interactions was not an “all-or-none” transition as it occurred through distinct two-step or single step pathways with or without intermediate states. The knob-hole bonds were stronger, tighter, and more brittle at pH 7 than at pH 5. The B:b knob-hole bonds were weaker, looser, and more compliant than the A:a knob-hole bonds at pH 7 but stronger, tighter, and less compliant at pH 5. Surprisingly, the knob-hole bonds were stronger, not weaker, at elevated temperature (T = 37 °C) compared with T = 25 °C due to the helix-to-coil transition in loop I that helps stabilize the bonds. These results provide detailed qualitative and quantitative characteristics underlying the most significant non-covalent interactions involved in fibrin polymerization.     

Conformational Preference of ‘CαNN’ Short Peptide Motif towards Recognition of Anions

Among several ‘anion binding motifs’, the recently described ‘C^αNN’ motif occurring in the loop regions preceding a helix, is conserved through evolution both in sequence and its conformation. To establish the significance of the conserved sequence and their intrinsic affinity for anions, a series of peptides containing the naturally occurring ‘C^αNN’ motif at the N-terminus of a designed helix, have been modeled and studied in a context free system using computational techniques. Appearance of a single interacting site with negative binding free-energy for both the sulfate and phosphate ions, as evidenced in docking experiments, establishes that the ‘C^αNN’ segment has an intrinsic affinity for anions. Molecular Dynamics (MD) simulation studies reveal that interaction with anion triggers a conformational switch from non-helical to helical state at the ‘C^αNN’ segment, which extends the length of the anchoring-helix by one turn at the N-terminus. Computational experiments substantiate the significance of sequence/structural context and justify the conserved nature of the ‘C^αNN’ sequence for anion recognition through “local” interaction.     

Changes in Eating Attitudes,Body Esteem and Weight Control Behaviours during Adolescence in a South African Cohort

Failure to consume an adequate diet or over consumption during adolescence can disrupt normal growth and development, resulting in undesirable weight change. This leads to an increase in unhealthy weight control practices related to eating and exercise among both adolescent girls and boys to meet the societal ‘ideal’ body shape. This study therefore aims to examine the longitudinal changes in eating attitudes, body-esteem and weight control behaviours among adolescents between 13 and 17 years; and, to describe perceptions around body shape at age 17 years. A total of 1435 urban South African black and mixed ancestry boys and girls, who had data at both age 13 and 17 years from the Birth to Twenty cohort were included. Data were collected through self-administered questionnaires on eating attitudes (EAT-26), body esteem and weight control behaviours for either weight loss or muscle gain attempts. Height and weight were measured at both time points and BMI was calculated. Black females had a higher BMI (p<0.001) and an increased risk of developing eating disorders as well as significant increase in the prevalence of weight loss practices between the ages 13 and 17 years. At age 17 years both Mixed ancestry adolescents had lower body-esteem compared to black adolescents. The prevalence of possible eating disorders was 11% and 13.1% in early and late adolescents respectively. Males and females shared similar opinions on normal silhouettes being the ‘best’, ‘getting respect’ and being the ‘happiest’, while the obese silhouette was associated with the ‘worst’ and the ‘unhappiest’, and the underweight silhouette with the “weakest”. Black females had a higher BMI and an increased risk of developing eating disorders. Adolescent females engaged more in weight loss practices whereas, males in muscle gain practices indicating that Western norms of thinness as the ideal are becoming more common in South Africa.