Recombinational DNA double-strand breaks in mice precede synapsis

In Saccharomyces cerevisiae, meiotic recombination is initiated by Spo11-dependent double-strand breaks (DSBs), a process that precedes homologous synapsis. Here we use an antibody specific for a phosphorylated histone (gamma-H2AX, which marks the sites of DSBs) to investigate the timing, distribution and Spo11-dependence of meiotic DSBs in the mouse. We show that, as in yeast, recombination in the mouse is initiated by Spo11-dependent DSBs that form during leptotene. Loss of gamma-H2AX staining (which in irradiated somatic cells is temporally linked with DSB repair) is temporally and spatially correlated with synapsis, even when this synapsis is 'non-homologous'.     

Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis

Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the inflammatory response of macrophages and T cells, oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue repair including expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective and regenerative roles in the brain. Received 31 October 2002; received after revision 23 November 2002; accepted 26 November 2002 RID="*" ID="*"Corresponding author. M. Penkowa and C. Espejo contributed equally to this paper.     

Large Cretaceous sphenodontian from Patagonia provides insight into lepidosaur evolution in Gondwana

Sphenodontian reptiles successfully radiated during Triassic and Jurassic times, but were driven almost to extinction during the Cretaceous period. The sparse Early Cretaceous record of sphenodontians has been interpreted as reflecting the decline of the group in favour of lizards, their suspected ecological successors. However, recent discoveries in Late Cretaceous beds in Patagonia partially modify this interpretation. Numerous skeletons of a new sphenodontian, Priosphenodon avelasi gen. et sp. nov., were collected from a single locality in the Cenomanian-Turonian Candeleros Formation, where it is more abundant than any other tetrapod group recorded in the quarry (for example, Crocodyliformes, Serpentes, Dinosauria and Mammalia). Adult specimens of Priosphenodon reached one metre in length, larger than any previously known terrestrial sphenodontian. Here we propose, using available evidence, that sphenodontians were not a minor component of the Cretaceous terrestrial ecosystems of South America, and that their ecological replacement by squamates was delayed until the early Tertiary. The new discovery helps to bridge the considerable gap in the fossil record (around 120 million years) that separates the Early Cretaceous sphenodontians from their living relatives (Sphenodon).     

Heart rate variability during high-intensity exercise

The aim of this paper is to describe and analyse the behaviour of heart rate variability (HRV) during constant-load, high-intensity exercise using a time frequency analysis (Wavelet Transform). Eleven elite cyclists took part in the study (age: 18.6±3.0 years; VO_2max: 4.88±0.61 litres·min^?1). Initially, all subjects performed an incremental cycloergometer test to determine load power in a constant load-test (379.55±36.02 W; 89.0%). HRV declined dramatically from the start of testing (p <0.05). The behaviour of power spectral density within the LF band mirrored that of total energy, recording a significant decrease from the outset LF peaks fell rapidly thereafter, remaining stable until the end of the test. HF-VHF fell sharply in the first 20 to 30 seconds. The relative weighting (%) of HF-VHF was inverted with the onset of fatigue, [1.6% at the start, 7.1 (p <0.05) at the end of the first phase, and 43.1% (p <0.05) at the end of the test]. HF-VHF_peak displayed three phases: a moderate initial increase, followed by a slight fall, thereafter increasing to the end of the test. The LF/HF-VHF ratio increased at the start, later falling progressively until the end of the first phase and remaining around minimal values until the end of the test.     

The novel Cer-like protein Caronte mediates the establishment of embryonic left-right asymmetry.

In the chick embryo, left-right asymmetric patterns of gene expression in the lateral plate mesoderm are initiated by signals located in and around Hensen's node. Here we show that Caronte (Car), a secreted protein encoded by a member of the Cerberus/Dan gene family, mediates the Sonic hedgehog (Shh)-dependent induction of left-specific genes in the lateral plate mesoderm. Car is induced by Shh and repressed by fibroblast growth factor-8 (FGF-8). Car activates the expression of Nodal by antagonizing a repressive activity of bone morphogenic proteins (BMPs). Our results define a complex network of antagonistic molecular interactions between Activin, FGF-8, Lefty-1, Nodal, BMPs and Car that cooperate to control left-right asymmetry in the chick embryo.