Biological aspects of Cuvier’s beaked whale (Ziphius cavirostris) recorded in the Croatian part of the Adriatic Sea

The paper describes two stranded ziphiids from Croatia: a subadult female (length 430 cm, body mass 610 kg) that was stranded in 2001 and an adult male (length 510 cm, body mass ∼1,000 kg) that was stranded in 2002. Both were confirmed to be Cuvier’s beaked whales (Ziphius cavirostris Cuvier, 1823) from analysis of mitochondrial DNA sequences and osteological features. There are no previous records of Cuvier’s beaked whales from the Croatian part of the Adriatic. The external shape of the head of the female specimen appears to be significantly different from the heads of Cuvier’s beaked whales from other seas. The Croatian specimen exhibited embedded pieces of gravel in the gum tissue around the tip of the lower and upper jaws, which was observed for the first time in a Cuvier’s beaked whale. The presence of the female in shallow coastal waters for several weeks and her boat-positive behaviour are apparently also first records of this kind for the species. The female was found to have ingested several plastic bags which likely caused her death. These are the northernmost findings of this species in the Adriatic Sea.     

Linking animal models to human congenital diaphragmatic hernia

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a major life-threatening malformation, occurring in approximately 1 in 3,000 live births. Over the years, different animal models have been used to gain insight into the etiology of this complex congenital anomaly and to develop treatment strategies. However, to date the pathogenic mechanism is still not understood, and treatment remains difficult because of the associated pulmonary hypoplasia and pulmonary hypertension. METHODS: In this review, data available from several animal models will be discussed. The retinoic acid signaling pathway (RA pathway, retinoid pathway) will be addressed as a developmental pathway that is potentially disrupted in the pathogenesis of CDH. Furthermore, genetic factors involved in diaphragm and lung development will be discussed. CONCLUSIONS: With this review article, we aim to provide a concise overview of the current most important experimental genetic data available in the field of CDH.     

Associations of Lifestyle Factors,Disease History and Awareness with Health-Related Quality of Life in a Thai Population

Background

The impact of the presence and awareness of individual health states on quality of life (HRQoL) is often documented. However, the impacts of different health states have rarely been compared amongst each other, whilst quality of life data from Asia are relatively sparse. We examined and compared the effects of different health states on quality of life in a Thai population.

Methods

In 2008–2009, 5,915 corporate employees were invited to participate in a survey where HRQoL was measured by the Short Form 36 (SF-36) questionnaire. The adjusted mean SF-36 scores were calculated for each self-reported illness, number of chronic conditions, lifestyle factors and awareness of diabetes and hypertension. The effect sizes (ES) were compared using Cohen''s d.

Results

The response rate was 82% and 4,683 (79.1%) had complete data available for analysis. Physical and Mental Component Summary (PCS and MCS) scores decreased as the number of chronic conditions increased monotonically (p<0.0001). Diabetes and hypertension negatively influenced PCS (mean score differences −0.6 and −1.5, p<0.001 respectively) but not MCS, whereas awareness of diabetes and hypertension negatively influenced MCS (−2.9 and −1.6, p<0.005 respectively) but not PCS. Arthritis had the largest ES on PCS (−0.37), while awareness of diabetes had the largest ES on MCS (−0.36). CVD moderately affected PCS and MCS (ES −0.34 and −0.27 respectively). Obesity had a negative effect on PCS (ES −0.27). Exercise positively affected PCS and MCS (ES +0.08 and +0.21 (p<0.01) respectively).

Conclusion

Health promotion to reduce the prevalence of chronic diseases is important to improve the quality of life in Asian populations. Physical activity is an important part of such programs. Awareness of diseases may have greater impacts on mental health than having the disease itself. This has implications for the evaluation of the cost-benefit of screening and labeling of individuals with pre-disease states.     

Development and validation of a risk prediction model of preterm birth for women with preterm labour symptoms (the QUIDS study): A prospective cohort study and individual participant data meta-analysis

BackgroundTimely interventions in women presenting with preterm labour can substantially improve health outcomes for preterm babies. However, establishing such a diagnosis is very challenging, as signs and symptoms of preterm labour are common and can be nonspecific. We aimed to develop and externally validate a risk prediction model using concentration of vaginal fluid fetal fibronectin (quantitative fFN), in combination with clinical risk factors, for the prediction of spontaneous preterm birth and assessed its cost-effectiveness.Methods and findingsPregnant women included in the analyses were 22⁺⁰ to 34⁺⁶ weeks gestation with signs and symptoms of preterm labour. The primary outcome was spontaneous preterm birth within 7 days of quantitative fFN test. The risk prediction model was developed and internally validated in an individual participant data (IPD) meta-analysis of 5 European prospective cohort studies (2009 to 2016; 1,783 women; mean age 29.7 years; median BMI 24.8 kg/m²; 67.6% White; 11.7% smokers; 51.8% nulliparous; 10.4% with multiple pregnancy; 139 [7.8%] with spontaneous preterm birth within 7 days). The model was then externally validated in a prospective cohort study in 26 United Kingdom centres (2016 to 2018; 2,924 women; mean age 28.2 years; median BMI 25.4 kg/m²; 88.2% White; 21% smokers; 35.2% nulliparous; 3.5% with multiple pregnancy; 85 [2.9%] with spontaneous preterm birth within 7 days). The developed risk prediction model for spontaneous preterm birth within 7 days included quantitative fFN, current smoking, not White ethnicity, nulliparity, and multiple pregnancy. After internal validation, the optimism adjusted area under the curve was 0.89 (95% CI 0.86 to 0.92), and the optimism adjusted Nagelkerke R² was 35% (95% CI 33% to 37%). On external validation in the prospective UK cohort population, the area under the curve was 0.89 (95% CI 0.84 to 0.94), and Nagelkerke R² of 36% (95% CI: 34% to 38%). Recalibration of the model’s intercept was required to ensure overall calibration-in-the-large. A calibration curve suggested close agreement between predicted and observed risks in the range of predictions 0% to 10%, but some miscalibration (underprediction) at higher risks (slope 1.24 (95% CI 1.23 to 1.26)). Despite any miscalibration, the net benefit of the model was higher than “treat all” or “treat none” strategies for thresholds up to about 15% risk. The economic analysis found the prognostic model was cost effective, compared to using qualitative fFN, at a threshold for hospital admission and treatment of ≥2% risk of preterm birth within 7 days. Study limitations include the limited number of participants who are not White and levels of missing data for certain variables in the development dataset.ConclusionsIn this study, we found that a risk prediction model including vaginal fFN concentration and clinical risk factors showed promising performance in the prediction of spontaneous preterm birth within 7 days of test and has potential to inform management decisions for women with threatened preterm labour. Further evaluation of the risk prediction model in clinical practice is required to determine whether the risk prediction model improves clinical outcomes if used in practice.Trial registrationThe study was approved by the West of Scotland Research Ethics Committee (16/WS/0068). The study was registered with ISRCTN Registry (ISRCTN 41598423) and NIHR Portfolio (CPMS: 31277).

Sarah J Stock and colleagues develop and validate a risk prediction model of spontaneous preterm birth for women with preterm labour symptoms, based on vaginal fluid fetal fibronectin and clinical risk factors.     

Characteristics of Misclassified CT Perfusion Ischemic Core in Patients with Acute Ischemic Stroke

Background

CT perfusion (CTP) is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up.

Materials and Methods

This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0). Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT≥145%, aCBV<2.0 ml/100g and infarct on follow-up noncontrast CT) and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT) regions. False discovery ratio (FDR), defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT) were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests.

Results

Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml); median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml). Median FDR between patients was 62% (IQR:49%-80%). Median relative mean transit time was 243% (IQR:198%-289%) and 342% (IQR:249%-432%) for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.43–1.79) ml/100g (P<0.01) and 1.38 (IQR:1.15–1.49) ml/100g (P<0.01) for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly.

Conclusion

For all patients a considerable region of the CTP ischemic core is misclassified. CTP parameters significantly differed between ischemic lesion agreement and misclassified CTP ischemic core, suggesting that CTP analysis may benefit from revisions.     

APPEARANCE, DISTRIBUTION, AND GENETIC DISTINCTIVENESS OF LONGMAN'S BEAKED WHALE, INDOPACETUS PACIFICUS

Longman's beaked whale, Indopacetus pacificus , was known previously from only two skulls. Here we describe four new specimens of this species from strandings in the western and central Indian Ocean. Two juveniles, previously misidentified from external morphology as Hyperoodon planifrons , were identified as I. pacificus through diagnostic characteristics of mitochondrial (mt) DNA sequences derived from the holotype of this species. Images of the external appearance and teeth of the species are presented for the first time. Comparison of the color pattern of these new specimens with that of "tropical bottlenose whales" sighted in the tropical Indian and Pacific oceans confirm that those unidentified whales represent I. pacificus. Moore (1968) erected a new genus, Indopacetus , for this species (described initially as Mesoplodon pacificus ) based primarily on cranial morphology. Phylogenetic analyses of short mtDNA fragments available from the specimens known to date were unable to resolve the validity of this genus. However, the diagnostic osteological features highlighted by Moore (1968) for Indopacetus were also observed in the new specimens. Rib count and number of fused cervical vertebrae may also be diagnostic. Rostrum depth at mid-length and melon shape further distinguish this species from Mesoplodon beaked whales. As such, we see no reason on morphological grounds to overturn Moore's (1968) proposal that Longman's beaked whale is sufficiently distinct to be afforded its own genus.     

Multivalent presentation of the cell-penetrating peptide nona-arginine on a linear scaffold strongly increases its membrane-perturbing capacity

Arginine-rich cell-penetrating peptides (CPP) are widely employed as delivery vehicles for a large variety of macromolecular cargos. As a mechanism-of-action for induction of uptake cross-linking of heparan sulfates and interaction with lipid head groups have been proposed. Here, we employed a multivalent display of the CPP nona-arginine (R9) on a linear dextran scaffold to assess the impact of heparan sulfate and lipid interactions on uptake and membrane perturbation. Increased avidity through multivalency should potentiate molecular phenomena that may only play a minor role if only individual peptides are used. To this point, the impact of multivalency has only been explored for dendrimers, CPP-decorated proteins and nanoparticles. We reasoned that multivalency on a linear scaffold would more faithfully mimic the arrangement of peptides at the membrane at high local peptide concentrations. On average, five R9 were coupled to a linear dextran backbone. The conjugate displayed a direct cytoplasmic uptake similar to free R9 at concentrations higher than 10 μM. However, this uptake was accompanied by an increased membrane disturbance and cellular toxicity that was independent of the presence of heparan sulfates. In contrast, for erythrocytes, the multivalent conjugate induced aggregation, however, showed only limited membrane perturbation. Overall, the results demonstrate that multivalency of R9 on a linear scaffold strongly increases the capacity to interact with the plasma membrane. However, the induction of membrane perturbation is a function of the cellular response to peptide binding.     

Ubiquitination by the Membrane-associated RING-CH-8 (MARCH-8) Ligase Controls Steady-state Cell Surface Expression of Tumor Necrosis Factor-related Apoptosis Inducing Ligand (TRAIL) Receptor 1

The eleven members of the membrane-associated RING-CH (MARCH) ubiquitin ligase family are relatively unexplored. Upon exogenous (over)expression, a number of these ligases can affect the trafficking of membrane molecules. However, only for MARCH-1 endogenous functions have been demonstrated. For the other endogenous MARCH proteins, no functions or substrates are known. We report here that TRAIL-R1 is a physiological substrate of the endogenous MARCH-8 ligase. Human TRAIL-R1 and R2 play a role in immunosurveillance and are targets for cancer therapy, because they selectively induce apoptosis in tumor cells. We demonstrate that TRAIL-R1 is down-regulated from the cell surface, with great preference over TRAIL-R2, by exogenous expression of MARCH ligases that are implicated in endosomal trafficking, such as MARCH-1 and -8. MARCH-8 attenuated TRAIL-R1 cell surface expression and apoptosis signaling by virtue of its ligase activity. This suggested that ubiquitination of TRAIL-R1 was instrumental in its down-regulation by MARCH-8. Indeed, in cells with endogenous MARCH expression, TRAIL-R1 was ubiquitinated at steady-state, with the conserved membrane-proximal lysine 273 as one of the potential acceptor sites. This residue was also essential for the interaction of TRAIL-R1 with MARCH-1 and MARCH-8 and its down-regulation by these ligases. Gene silencing identified MARCH-8 as the endogenous ligase that ubiquitinates TRAIL-R1 and attenuates its cell surface expression. These findings reveal that endogenous MARCH-8 regulates the steady-state cell surface expression of TRAIL-R1.     

Structural and functional responses of plant communities to climate change‐mediated alterations in the hydrology of riparian areas in temperate Europe

The hydrology of riparian areas changes rapidly these years because of climate change‐mediated alterations in precipitation patterns. In this study, we used a large‐scale in situ experimental approach to explore effects of drought and flooding on plant taxonomic diversity and functional trait composition in riparian areas in temperate Europe. We found significant effects of flooding and drought in all study areas, the effects being most pronounced under flooded conditions. In near‐stream areas, taxonomic diversity initially declined in response to both drought and flooding (although not significantly so in all years) and remained stable under drought conditions, whereas the decline continued under flooded conditions. For most traits, we found clear indications that the functional diversity also declined under flooded conditions, particularly in near‐stream areas, indicating that fewer strategies succeeded under flooded conditions. Consistent changes in community mean trait values were also identified, but fewer than expected. This can have several, not mutually exclusive, explanations. First, different adaptive strategies may coexist in a community. Second, intraspecific variability was not considered for any of the traits. For example, many species can elongate shoots and petioles that enable them to survive shallow, prolonged flooding but such abilities will not be captured when applying mean trait values. Third, we only followed the communities for 3 years. Flooding excludes species intolerant of the altered hydrology, whereas the establishment of new species relies on time‐dependent processes, for instance the dispersal and establishment of species within the areas. We expect that altered precipitation patterns will have profound consequences for riparian vegetation in temperate Europe. Riparian areas will experience loss of taxonomic and functional diversity and, over time, possibly also alterations in community trait responses that may have cascading effects on ecosystem functioning.