Hox gene colinear expression in the avian medulla oblongata is correlated with pseudorhombomeric domains

The medulla oblongata (or caudal hindbrain) is not overtly segmented, since it lacks observable interrhombomeric boundaries. However, quail-chick fate maps showed that it is formed by 5 pseudorhombomeres (r7-r11) which were empirically found to be delimited consistently at planes crossing through adjacent somites (Cambronero and Puelles, 2000). We aimed to reexamine the possible segmentation or rostrocaudal regionalisation of this brain region attending to molecular criteria. To this end, we studied the expression of Hox genes from groups 3 to 7 correlative to the differentiating nuclei of the medulla oblongata. Our results show that these genes are differentially expressed in the mature medulla oblongata, displaying instances of typical antero-posterior (3′ to 5′) Hox colinearity. The different sensory and motor columns, as well as the reticular formation, appear rostrocaudally regionalised according to spaced steps in their Hox expression pattern. The anterior limits of the respective expression domains largely fit boundaries defined between the experimental pseudorhombomeres. Therefore the medulla oblongata shows a Hox-related rostrocaudal molecular regionalisation comparable to that found among rhombomeres, and numerically consistent with the pseudorhombomere list. This suggests that medullary pseudorhombomeres share some AP patterning mechanisms with the rhombomeres present in the rostral, overtly-segmented hindbrain, irrespective of variant boundary properties.     

Helix Dynamics in LacY: Helices II and IV

Biochemical and biophysical studies based upon crystal structures of both a mutant and wild-type lactose permease from Escherichia coli (LacY) in an inward-facing conformation have led to a model for the symport mechanism in which both sugar and H⁺ binding sites are alternatively accessible to both sides of the membrane. Previous findings indicate that the face of helix II with Asp68 is important for the conformational changes that occur during turnover. As shown here, replacement of Asp68 at the cytoplasmic end of helix II, particularly with Glu, abolishes active transport but the mutants retain the ability to bind galactopyranoside. In the x-ray structure, Asp68 and Lys131 (helix IV) lie within ∼ 4.2 Å of each other. Although a double mutant with Cys replacements at both position 68 and position 131 cross-links efficiently, single replacements for Lys131 exhibit very significant transport activity. Site-directed alkylation studies show that sugar binding by the Asp68 mutants causes closure of the cytoplasmic cavity, similar to wild-type LacY; however, strikingly, the probability of opening the periplasmic pathway upon sugar binding is markedly reduced. Taken together with results from previous mutagenesis and cross-linking studies, these findings lead to a model in which replacement of Asp68 blocks a conformational transition involving helices II and IV that is important for opening the periplasmic cavity. Evidence suggesting that movements of helices II and IV are coupled functionally with movements in the pseudo-symmetrically paired helices VIII and X is also presented.     

Xenopus Brachyury regulates mesodermal expression of Zic3, a gene controlling left-right asymmetry

The Brachyury gene has a critical role in the formation of posterior mesoderm and notochord in vertebrate development. A recent study showed that Brachyury is also responsible for the formation of the left-right (L-R) axis in mouse and zebrafish. However, the role of Brachyury in L-R axis specification is still elusive. Here, it is demonstrated that Brachyury is involved in L-R specification of the Xenopus laevis embryo and regulates expression of Zic3, which controls the L-R specification process. Overexpression of Xenopus Brachyury (Xbra) and dominant-negative type Xbra (Xbra-EnR) altered the orientation of heart and gut looping, concomitant with disturbed laterality of nodal-related 1 (Xnr1) and Pitx2 expression, both of which are normally expressed in the left lateral plate mesoderm. Furthermore, activation of inducible type Xbra (Xbra-GR) induces Zic3 expression within 20 min. These results suggest that a role of Brachyury in L-R specification may be the direct regulation of Zic3 expression.     

Right ventricular collagen and fibronectin levels in patients with pulmonary atresia and ventricular septal defect

Pulmonary atresia (PA) with ventricular septal defect (VSD) is an extreme form of tetralogy of Fallot with characteristic right ventricular hypertrophy. To reduce the right ventricular overload, these children have to undergo staged corrective surgery to restore physiological pulmonary perfusion. We studied the degree of fibrosis by analysing the myocardial expression pattern (at mRNA and protein level) of the extracellular matrix proteins, collagen and fibronectin in biopsies taken at corrective surgery from 14 patients affected by PA,VSD. Expression analysis by RT-PCR showed significantly higher levels for collagen III (p = 0.03), whereas collagen I (p = 0.31) and fibronectin (p = 0.47) mRNA levels remained unaltered in PA, VSD patients as compared to age matched controls. Video image analysis of immunohistochemical staining showed unchanged interstitial levels for total collagen (p = 0.17) as well as for fibronectin (p = 0.13) in the patients with PA, VSD. However, peri-vascular staining for collagen (p < 0.01) and fibronectin (p = 0.02) represented as the peri-vascular stained area corrected for the vessel lumen area showed significantly decreased levels in the PA,VSD group as compared to controls. Our results indicate that the patients with PA, VSD have inadequate extracellular matrix support for their coronary blood vessels and perhaps due to an altered biosynthesis of collagen and fibronectin network.     

A curve-free method for phase I clinical trials

Consider the problem of finding the dose that is as high as possible subject to having a controlled rate of toxicity. The problem is commonplace in oncology Phase I clinical trials. Such a dose is often called the maximum tolerated dose (MTD) since it represents a necessary trade-off between efficacy and toxicity. The continual reassessment method (CRM) is an improvement over traditional up-and-down schemes for estimating the MTD. It is based on a Bayesian approach and on the assumption that the dose-toxicity relationship follows a specific response curve, e.g., the logistic or power curve. The purpose of this paper is to illustrate how the assumption of a specific curve used in the CRM is not necessary and can actually hinder the efficient use of prior inputs. An alternative curve-free method in which the probabilities of toxicity are modeled directly as an unknown multidimensional parameter is presented. To that purpose, a product-of-beta prior (PBP) is introduced and shown to bring about logical improvements. Practical improvements are illustrated by simulation results.     

OCCURRENCE, COMPOSITION, AND POTENTIAL FUNCTIONS OF NORTH ATLANTIC RIGHT WHALE (EUBALAENA GLACIALIS) SURFACE ACTIVE GROUPS

Marine mammal social interactions are poorly understood primarily because of the difficulty of observing these behaviors in the wild. Observations of copulations in North Atlantic right whale surface active groups (SAGs) have led to the hypothesis that the function of these groups is for conception. The occurrence and composition of SAGs sighted from 1992 to 2001 were investigated on the basis of age, sex, and reproductive status of individuals. A total of 918 SAG events were documented. SAGs were observed in all habitat areas and in all months in which right whales were sighted. Group compositions revealed both potentially conceptive groups and nonconceptive groups. Of right whales whose age was known, 93% were first sighted in SAGs as juveniles, and more than half of all observed groups contained at least one juvenile whale. The group composition and timing of occurrence of SAGs do not support the hypothesis that all groups serve a purely conceptive function. Their functional role is likely much broader. Other potential functions include play, mating practice, or maintenance of social bonds.     

“The national music scene”: the analysis of the Nazi rock discourse and its relationship with the upsurge of nationalism in Poland

The article contains the analysis of lyrics created by bands associated with the “national music scene” in Poland, as well as the means of fascist propaganda used in music by far-right extremists. The article also shows the cultural and political similarities between the official right in Poland (PiS party) and extreme right wing movements. These environments are bridged by a similar cultural narrative, which is based on the cult of the nation and tradition, a dislike for immigrants, as well as the creation of conspiracy myths concerning “traitors of the homeland”.     

Constructing common sense: Language and ethnicity in Ukrainian public discourse

Immigrant integration policies are commonly assumed to be shaped by traditional understandings of citizenship and belonging. Accordingly, such policy frameworks are considered path-dependent and thus stable over time. The recent surge of radical right anti-immigrant parties in many Western European countries challenges this stability-thesis. Several scholars contend that this change in the party political landscape caused an illiberal turn, resulting in more restrictive integration policies. This paper tests whether integration policies are indeed challenged by radical right parties, or whether they remain path-dependent policy frameworks, using subnational comparative analysis. The results of our cross-sectional regression analysis over twenty six Swiss cantons reveal that cantonal integration policies reflect clear patterns of regional citizenship culture, suggesting that they remain stable policy frameworks. By contrast, the considerable electoral success of the right populist Swiss People's Party (SVP) over the last two decades did not directly result in more restrictive cantonal integration policies.     

A Swedish subfossil find of a bowhead whale from the late Pleistocene: shore displacement,paleoecology in south-west Sweden and the identity of the Swedenborg whale (Balaena swedenborgii Liljeborg, 1867)

The Swedenborg whale Balaena swedenborgii Liljeborg, 1867, is a baleen whale species believed to have existed in the North Sea from the period when the inland ice melted around 13,000 before present (BP) until about 8000 years ago. The first bones attributed to this species were found in Sweden in 1705. When whale remains were discovered on the Swedish west coast during the extension work of a motorway extension, it was speculated that this could be a specimen of the extinct Swedenborg whale. The bones were found 72 m above the present-day sea level embedded in glacial mud. Shelly remains of marine organisms were present in the deposit surrounding the whale-fall, and sediments with the associated specimens were therefore collected for further analyses. We applied radiocarbon dating, thin sectioning, morphological analyses, ancient DNA typing and analyses of the associated shelly assemblage in an interdisciplinary effort to understand the circumstances of this fossil whale-fall. Our results show that the whale is not the putative species B. swedenborgii, but a bowhead whale Balaena mysticetus. The results also indicate that the whale must have been rapidly covered by glacial sediments, highlighting the speed of the deglacial process in the area.