Tracing transitions : an overview of the evolution and migrations of the genus Mammuthus BROOKES, 1828 (Mammalia, Proboscidea)

The text mainly deals with the Eurasian evolutionary history of mammoths. It focuses on the time bracket 1.0-0.6 Ma, within which Mammuthus meridionalis (the southern mammoth) finally became extinct in Europe. Its descendant,the initially eastern Asian steppe mammoth (M. trogontherii) was a comparatively late immigrant in Europe (c. 1.2-1.0 Ma)and then for a time was the only mammoth species there. European sites that yielded relevant material are rivised. The probability of hybridisation between the said species, suggested by the occurrence of so-called mosaic molars, is discussed. In addition, a number of subspecific taxa traditionally referred to M. meridionalis is now ascribed to M. trogontherii, which reduces the role played by M. meridionalis at the end of the Early Pleistocene.LEI Universiteit LeidenArcheobotan

Validation and application of intravascular ultrasound in endovascular treatment of abdominal aortic aneurysm

An abdominal aortic aneurysm (AAA) is a localized and permanent dilatation of the aorta that presents a clear danger for the patient because of the risk of rupture. The chance of rupture increases with the size of the aneurysm. Mortality after rupture is high: 60-70% of patients with a ruptured AAA will not reach the hospital alive. Furthermore, surgical treatment of ruptured AAA carries an additional mortality of 45-55%. Because of the poor prognosis of ruptured AAA, prophylactic exclusion of AAA is performed for AAA larger than 5.0 to 5.5 cm in diameter. The standard way of treating AAA is by elective open surgery. In this procedure, the diseased aortic segment is opened after proximal and distal cleaning of the vessel and the contents of the aneurysm are removed. A synthetic prosthesis is placed inside the aneurysm. The proximal and distal ends of the prosthesis are anastomosed via continuous sutures to the normal aorta and/or iliac arteries, after which the aneurysm wall is closed around the prosthesis. Elective surgery itself carries a mortality of 5_7% ,patients aged over 70 years, patients with congestive heart failure, cardiac ischemia, preexistent dysrythmia, renal impairment or pulmonary impairment are known to have an increased mortality

Intravascular ultrasound evidence for coarctation causing symptomatic renal artery stenosis

BACKGROUND: A recent study of human cadaveric renal arteries revealed that renal artery narrowing could be due not only to atherosclerotic plaque compensated for by adaptive remodeling, but also to hitherto undescribed focal narrowing of an otherwise normal renal arterial wall (ie, coarctation). The present study investigated whether vessel coarctation could be identified in patients with symptomatic renal artery stenosis (RAS). METHODS AND RESULTS: Consecutive symptomatic patients with angiographically proven atherosclerotic RAS who were referred for stent placement were studied by 30-MHz intravascular ultrasound before intervention (n=18) or after predilatation (n=18). Analysis included assessment of the media-bounded area and plaque area (PLA) at the most stenotic site and at a distal reference site (most distal cross-section in the main renal artery with normal appearance). Coarctation was considered present whenever the target/reference media-bounded area was </=85%. Before intervention, coarctation was observed in 9 of 18 patients and adaptive remodeling in 9 of 18 patients. Coarctation lesions had a significantly smaller PLA than adaptive remodeled lesions (P=0.001). Similarly, despite predilatation, coarctation was seen in 8 of 18 patients who had significantly smaller PLAs (P=0. 008) when compared with those patients who had adaptive remodeled lesions. No differences in severity of RAS or angiographic or clinical parameters were observed. CONCLUSIONS: Low-plaque coarctation may cause a considerable proportion of symptomatic RAS, which is angiographically and clinically indistinguishable from plaque-rich RAS

Continental drift: connecting Great Britain and Scandinavia

Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

MAP3K8 (TPL2/COT) Affects Obesity-Induced Adipose Tissue Inflammation without Systemic Effects in Humans and in Mice

Chronic low-grade inflammation in adipose tissue often accompanies obesity, leading to insulin resistance and increasing the risk for metabolic diseases. MAP3K8 (TPL2/COT) is an important signal transductor and activator of pro-inflammatory pathways that has been linked to obesity-induced adipose tissue inflammation. We used human adipose tissue biopsies to study the relationship of MAP3K8 expression with markers of obesity and expression of pro-inflammatory cytokines (IL-1ß, IL-6 and IL-8). Moreover, we evaluated obesity-induced adipose tissue inflammation and insulin resistance in mice lacking MAP3K8 and WT mice on a high-fat diet (HFD) for 16 weeks. Individuals with a BMI >30 displayed a higher mRNA expression of MAP3K8 in adipose tissue compared to individuals with a normal BMI. Additionally, high mRNA expression levels of IL-1ß, IL-6 and IL-8, but not TNF -a, in human adipose tissue were associated with higher expression of MAP3K8. Moreover, high plasma SAA and CRP did not associate with increased MAP3K8 expression in adipose tissue. Similarly, no association was found for MAP3K8 expression with plasma insulin or glucose levels. Mice lacking MAP3K8 had similar bodyweight gain as WT mice, yet displayed lower mRNA expression levels of IL-1ß, IL-6 and CXCL1 in adipose tissue in response to the HFD as compared to WT animals. However, MAP3K8 deficient mice were not protected against HFD-induced adipose tissue macrophage infiltration or the development of insulin resistance. Together, the data in both human and mouse show that MAP3K8 is involved in local adipose tissue inflammation, specifically for IL-1ß and its responsive cytokines IL-6 and IL-8, but does not seem to have systemic effects on insulin resistance

The clinical spectrum of limb girdle muscular dystrophy. A survey in the Netherlands

A cross-sectional study was performed in the Netherlands to define the clinical characteristics of the various subtypes within the broad and heterogeneous entity of limb girdle muscular dystrophy (LGMD). An attempt was made to include all known cases of LGMD in the Netherlands. Out of the reported 200 patients, 105 who fulfilled strictly defined criteria were included. Forty-nine patients, mostly suffering from dystrophinopathies and facioscapulohumeral muscular dystrophy, appeared to be misdiagnosed. Thirty-four cases were sporadic, 42 patients came from autosomal recessive and 29 from autosomal dominant families. The estimated prevalence of LGMD in the Netherlands was at least 8.1 x 10-6. The clinical features of the autosomal recessive and sporadic cases were indistinguishable from those of the autosomal dominant patients, although half hypertrophy was seen more frequently, and the course of the disease was more severe in autosomal recessive and sporadic cases. The pectoralis, iliopsoas and gluteal muscles, hip adductors and hamstrings were the most affected muscles. Distal muscle involvement occurred late in the course of the disease. Facial weakness was a rare phenomenon. The severity of the clinical picture was correlated with a deteriorating lung function. All autosomal dominantly inherited cases showed a mild course, although in two families life-expectancy was reduced because of concomitant cardiac involvement

Heterogeneous clinical phenotypes and cerebral malformations reflected by rotatin cellular dynamics

Recessive mutations in RTTN, encoding the protein rotatin, were originally identified as cause of polymicrogyria, a cortical malformation. With time, a wide variety of other brain malformations has been ascribed to RTTN mutations, including primary microcephaly. Rotatin is a centrosomal protein possibly involved in centriolar elongation and ciliogenesis. However, the function of rotatin in brain development is largely unknown and the molecular disease mechanism underlying cortical malformations has not yet been elucidated. We performed both clinical and cell biological studies, aimed at clarifying rotatin function and pathogenesis. Review of the 23 published and five unpublished clinical cases and genomic mutations, including the effect of novel deep intronic pathogenic mutations on RTTN transcripts, allowed us to extrapolate the core phenotype, consisting of intellectual disability, short stature, microcephaly, lissencephaly, periventricular heterotopia, polymicrogyria and other malformations. We show that the severity of the phenotype is related to residual function of the protein, not only the level of mRNA expression. Skin fibroblasts from eight affected individuals were studied by high resolution immunomicroscopy and flow cytometry, in parallel with in vitro expression of RTTN in HEK293T cells. We demonstrate that rotatin regulates different phases of the cell cycle and is mislocalized in affected individuals. Mutant cells showed consistent and severe mitotic failure with centrosome amplification and multipolar spindle formation, leading to aneuploidy and apoptosis, which could relate to depletion of neuronal progenitors often observed in microcephaly. We confirmed the role of rotatin in functional and structural maintenance of primary cilia and determined that the protein localized not only to the basal body, but also to the axoneme, proving the functional interconnectivity between ciliogenesis and cell cycle progression. Proteomics analysis of both native and exogenous rotatin uncovered that rotatin interacts with the neuronal (non-muscle) myosin heavy chain subunits, motors of nucleokinesis during neuronal migration, and in human induced pluripotent stem cell-derived bipolar mature neurons rotatin localizes at the centrosome in the leading edge. This illustrates the role of rotatin in neuronal migration. These different functions of rotatin explain why RTTN mutations can lead to heterogeneous cerebral malformations, both related to proliferation and migration defects.Genetics of disease, diagnosis and treatmen