Species specificity and sexual dimorphism in tooth shape among the three sympatric haplochromine species in Lake Kivu cichlids

Tooth shape is used to differentiate between morphologically similar species of vertebrates, including fish. This study aimed to quantify tooth shape of three sympatric species: Haplochromis kamiranzovu, H. insidiae, and H. astatodon endemic to Lake Kivu, whose existing identification criteria are currently only qualitative. A quantitative tooth shape analysis was performed based on digitized tooth outline data with a subsequent elliptic Fourier analysis to test for differences among the three species. We looked at crown shape and size differences within H. kamiranzovu and H. insidiae at geographical, habitat, and gender levels. No comparison at habitat level was done for H. astatodon because it is found only in littoral zone. The analysis revealed significant tooth shape differences among the three species. Haplochromis astatodon had a significantly longer major cusp height and a longer and larger minor cusp than that of H. insidiae. It had also a longer major cusp height and a longer and larger minor cusp than that of H. kamiranzovu. Tooth shape differences of H. kamiranzovu and H. insidiae species were not significantly different between littoral and pelagic fish (p > .05) while differences were significant between southern and northern Lake Kivu populations (p < .05). Tooth sizes in H. kamiranzovu and H. insidiae were significantly different, both in height and width as well as in their ratios, and this was true at sex and geographic levels (p < .05), but not at habitat level (p > .05). Tooth shape was also significantly different with sharp teeth for males compared with females of southern populations versus northern ones. These shape‐ and size‐related differences between sexes suggest differences in the foraging strategies toward available food resources in the lake habitat. Further research should explain the genetic basis of the observed pattern.     

Trophic divergence of Lake Kivu cichlid fishes along a pelagic versus littoral habitat axis

Local adaptation to the littoral and pelagic zones in two cichlid haplochromine fish species from Lake Kivu was investigated using morphometrics. Cranial variation and inferred jaw mechanics in both sexes of the two species across the two habitat types were quantified and compared. Comparisons of littoral versus pelagic populations revealed habitat‐specific differences in the shape of the feeding apparatus. Also, kinematic transmission of the anterior jaw four‐bar linkage that promotes greater jaw protrusion was higher in the pelagic zone than in the littoral zone for both species. Inferred bite force was likewise higher in pelagic zone fish. There were also sex‐specific differences in craniofacial morphology as males exhibited longer heads than females in both habitats. As has been described for other cichlids in the East African Great Lakes, local adaptation to trophic resources in the littoral and pelagic habitats characterizes these two Lake Kivu cichlids. Similar studies involving other types of the Lake Kivu fishes are recommended to test the evidence of the observed trophic patterns and their genetic basis of divergences.     

Identifying Emotions on the Basis of Neural Activation

We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame) while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1) neural activation of the same individual in other trials, 2) neural activation of other individuals who experienced similar trials, and 3) neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing.     

Establishment and Biological Characterization of a Panel of Glioblastoma Multiforme (GBM) and GBM Variant Oncosphere Cell Lines

Objective

Human tumor cell lines form the basis of the majority of present day laboratory cancer research. These models are vital to studying the molecular biology of tumors and preclinical testing of new therapies. When compared to traditional adherent cell lines, suspension cell lines recapitulate the genetic profiles and histologic features of glioblastoma multiforme (GBM) with higher fidelity. Using a modified neural stem cell culture technique, here we report the characterization of GBM cell lines including GBM variants.

Methods

Tumor tissue samples were obtained intra-operatively and cultured in neural stem cell conditions containing growth factors. Tumor lines were characterized in vitro using differentiation assays followed by immunostaining for lineage-specific markers. In vivo tumor formation was assayed by orthotopic injection in nude mice. Genetic uniqueness was confirmed via short tandem repeat (STR) DNA profiling.

Results

Thirteen oncosphere lines derived from GBM and GBM variants, including a GBM with PNET features and a GBM with oligodendroglioma component, were established. All unique lines showed distinct genetic profiles by STR profiling. The lines assayed demonstrated a range of in vitro growth rates. Multipotency was confirmed using in vitro differentiation. Tumor formation demonstrated histologic features consistent with high grade gliomas, including invasion, necrosis, abnormal vascularization, and high mitotic rate. Xenografts derived from the GBM variants maintained histopathological features of the primary tumors.

Conclusions

We have generated and characterized GBM suspension lines derived from patients with GBMs and GBM variants. These oncosphere cell lines will expand the resources available for preclinical study.     

Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity

The Drosophila melanogaster warts/lats tumour suppressor has two mammalian counterparts LATS1/Warts-1 and LATS2/Kpm. Here, we show that mammalian Lats orthologues exhibit distinct expression profiles according to germ cell layer origin. Lats2(-/-) embryos show overgrowth in restricted tissues of mesodermal lineage; however, lethality ultimately ensues on or before embryonic day 12.5 preceded by defective proliferation. Lats2(-/-) mouse embryonic fibroblasts (MEFs) acquire growth advantages and display a profound defect in contact inhibition of growth, yet exhibit defective cytokinesis. Lats2(-/-) embryos and MEFs display centrosome amplification and genomic instability. Lats2 localizes to centrosomes and overexpression of Lats2 suppresses centrosome overduplication induced in wild-type MEFs and reverses centrosome amplification inherent in Lats2(-/-) MEFs. These findings indicate an essential role of Lats2 in the integrity of processes that govern centrosome duplication, maintenance of mitotic fidelity and genomic stability.     

Regulation of plasmin activity by annexin II tetramer

Annexin II tetramer (AIIt) is a major Ca(2+)-binding protein of the endothelial cell surface which has been shown to stimulate the tissue plasminogen activator (t-PA)-dependent conversion of plasminogen to plasmin. In the present report, we have examined the regulation of plasmin activity by AIIt. The incubation of plasmin with AIIt resulted in a 95% loss in plasmin activity. SDS-PAGE analysis established that AIIt stimulated the autoproteolytic digestion of plasmin heavy and light chains. The kinetics of AIIt-stimulated plasmin autoproteolysis were first-order, suggesting that binding of plasmin to AIIt resulted in the spontaneous autoproteolysis of the bound plasmin. AIIt did not affect the activity of other serine proteases such as t-PA or urokinase-type plasminogen activator. Furthermore, other annexins such as annexin I, II, V, or VI did not stimulate plasmin autoproteolysis. Increasing the concentration of AIIt on the surface of human 293 epithelial cells increased cell-mediated plasmin autoproteolysis. Thus, in addition to stimulating the formation of plasmin, AIIt also promotes plasmin inactivation. These results therefore suggest that AIIt may function to provide the cell surface with a transient pulse of plasmin activity.     

Physician experience and outcomes among patients admitted to general internal medicine teaching wards

Background:

Physician scores on examinations decline with time after graduation. However, whether this translates into declining quality of care is unknown. Our objective was to determine how physician experience is associated with negative outcomes for patients admitted to hospital.

Methods:

We conducted a retrospective cohort study involving all patients admitted to general internal medicine wards over a 2-year period at all 7 teaching hospitals in Alberta, Canada. We used files from the Alberta College of Physicians and Surgeons to determine the number of years since medical school graduation for each patient’s most responsible physician. Our primary outcome was the composite of in-hospital death, or readmission or death within 30 days postdischarge.

Results:

We identified 10 046 patients who were cared for by 149 physicians. Patient characteristics were similar across physician experience strata, as were primary outcome rates (17.4% for patients whose care was managed by physicians in the highest quartile of experience, compared with 18.8% in those receiving care from the least experienced physicians; adjusted odds ratio [OR] 0.88, 95% confidence interval [CI] 0.72–1.06). Outcomes were similar between experience quartiles when further stratified by physician volume, most responsible diagnosis or complexity of the patient’s condition. Although we found substantial variability in length of stay between individual physicians, there were no significant differences between physician experience quartiles (mean adjusted for patient covariates and accounting for intraphysician clustering: 7.90 [95% CI 7.39–8.42] d for most experienced quartile; 7.63 [95% CI 7.13–8.14] d for least experienced quartile).

Interpretation:

For patients admitted to general internal medicine teaching wards, we saw no negative association between physician experience and outcomes commonly used as proxies for quality of inpatient care.Many jurisdictions have instituted compulsory recertification of physicians on the assumption that quality of care declines with experience. Although a systematic review reported that 32 of 62 studies found decreasing performance with increasing physician experience, most of these studies evaluated performance on examinations or hypothetical vignettes rather than actual quality of care provided to patients, and most of the studies were done decades ago, before the widespread availability of tools to readily facilitate evidence-based medicine.¹Experience is strongly related to better outcomes in surgery and obstetrics, but studies examining the association between physician experience and quality of care for medical patients have reported mixed results.^1–8 Many of the studies reporting an inverse association between experience and quality of care have focused on the provision of “guideline recommended tests or therapies” as a proxy for quality of care. However, guideline recommendations might not be appropriate in every situation.An evaluation of broader quality metrics may be more appropriate to answer this question. For example, in-hospital mortality and readmission rates or mortality postdischarge are commonly used as markers for quality of inpatient care, are endorsed by the Centers for Medicare & Medicaid Services and are included in the Patient Protection and Affordable Care Act.^9,10 However, to our knowledge, few studies have examined the association between these broader quality metrics and physician experience, and these studies have been limited. They either focused on single diagnoses,¹¹ excluded older adult patients,² examined data from only 1 hospital⁸ or combined data⁷ for both surgeons and physicians.Patients admitted to general internal medicine services at Alberta teaching hospitals are distributed between wards purely on the basis of bed availability, and attending physicians rotate every 1–4 weeks. For these reasons, the distribution of patients between attending physicians is quasirandom. We took advantage of this natural experiment to evaluate the association between attending physician experience (years since medical school graduation) and outcomes for patients admitted to general internal medicine wards in Alberta.     

Nuclear markers reveal that inter-lake cichlids' similar morphologies do not reflect similar genealogy

The apparent inter-lake morphological similarity among East African Great Lakes' cichlid species/genera has left evolutionary biologists asking whether such similarity is due to sharing of common ancestor or mere convergent evolution. In order to answer such question, we first used Geometric Morphometrics, GM, to quantify morphological similarity and then subsequently used Amplified Fragment Length Polymorphism, AFLP, to determine if similar morphologies imply shared ancestry or convergent evolution. GM revealed that not all presumed morphological similar pairs were indeed similar, and the dendrogram generated from AFLP data indicated distinct clusters corresponding to each lake and not inter-lake morphological similar pairs. Such results imply that the morphological similarity is due to convergent evolution and not shared ancestry. The congruency of GM and AFLP generated dendrograms imply that GM is capable of picking up phylogenetic signal, and thus GM can be potential tool in phylogenetic systematics.