Indications for a humid climate in the Western Desert of Egypt 11–10 Myr ago: evidence from Galagidae (Primates, Mammalia)

The timing of desertification of the Sahara Desert is poorly understood, with recent estimates indicating an onset of hyper-aridity during the Latest Miocene. Field work in Egypt in 2005 has led to the discovery of evidence that indicates that 11–10 Ma the Western Desert was covered in woodland. Fossiliferous cave breccia at Sheikh Abdallah, Western Desert, Egypt, has yielded a Late Miocene (11–10 Ma) microvertebrate fauna, which contains Galagidae, Microchiroptera, Macroscelididae, Soricidae, Erinaceidae, and Rodentia. The locality also yielded the remains of frogs, snakes, lizards, and birds. The fauna indicates a mean annual rainfall in excess of 500 mm and perhaps as much as 1,200 mm. This palaeoclimatic information is important because it reveals that the Sahara Desert, which is today the largest in the world, was either considerably smaller during the Late Miocene than it is today, or that it did not yet exist as a continuous hyper-arid belt right across the continent. This data accords with estimates of a Latest Miocene (8–7 Ma) increase in aridity in the Sahara. To cite this article: M. Pickford et al., C. R. Palevol 5 (2006).     

Implications for Collagen Binding from the Crystallographic Structure of Fibronectin 6FnI1�C2FnII7FnI

Collagen and fibronectin (FN) are two abundant and essential components of the vertebrate extracellular matrix; they interact directly with cellular receptors and affect cell adhesion and migration. Past studies identified a FN fragment comprising six modules, ⁶FnI^1–2FnII^7–9FnI, and termed the gelatin binding domain (GBD) as responsible for collagen interaction. Recently, we showed that the GBD binds tightly to a specific site within type I collagen and determined the structure of domains ^8–9FnI in complex with a peptide from that site. Here, we present the crystallographic structure of domains ⁶FnI^1–2FnII⁷FnI, which form a compact, globular unit through interdomain interactions. Analysis of NMR titrations with single-stranded collagen peptides reveals a dominant collagen interaction surface on domains ²FnII and ⁷FnI; a similar surface appears involved in interactions with triple-helical peptides. Models of the complete GBD, based on the new structure and the ^8–9FnI·collagen complex show a continuous putative collagen binding surface. We explore the implications of this model using long collagen peptides and discuss our findings in the context of FN interactions with collagen fibrils.     

Fossil leaves from Lukeino,a 6-million-year-old Formation in the Baringo Basin,Kenya

Thirty-eight dicotyledonous leaf morphotypes and some monocot leaf fragments are described from the Kapcharar, Kabogongoi, Koibo Chepkweny and Inoswa Kamelon localities in the upper third of the Lukeino Formation, Tugen Hills, Baringo Basin (Kenya). The leaves are preserved in fine-grained paper shales and range in length from 9 to 160 mm. Some of the leaves show affinities with extant species in the Burseraceae, Ebenaceae, Euphorbiaceae, Fabaceae, Loganiaceae, Malvaceae and Sapotaceae families that are common in the local flora today. There are compound and simple leaves, mostly entire-margined and with only 10% non-entire margins. A CLAMP analysis of the Kapcharar leaves indicates that the local climate was seasonal, summer wet with 1723 mm mean annual rainfall and with a mean annual temperature of 19.8 °C. The vegetation was a deciduous forest or woodland with open areas nearby. A monocot leaf and two fragments of fern pinnae are also described; they imply locally wetter environments. The flora described here is directly associated with the early hominid Orrorin tugenensis.     

Small molecules targeting hepatitis C virus-encoded NS5A cause subcellular redistribution of their target: insights into compound modes of action

The current standard of care for hepatitis C virus (HCV)-infected patients consists of lengthy treatment with interferon and ribavirin. To increase the effectiveness of HCV therapy, future regimens will incorporate multiple direct-acting antiviral (DAA) drugs. Recently, the HCV-encoded NS5A protein has emerged as a promising DAA target. Compounds targeting NS5A exhibit remarkable potency in vitro and demonstrate early clinical promise, suggesting that NS5A inhibitors could feature in future DAA combination therapies. Since the mechanisms through which these molecules operate are unknown, we have used NS5A inhibitors as tools to investigate their modes of action. Analysis of replicon-containing cells revealed dramatic phenotypic alterations in NS5A localization following treatment with NS5A inhibitors; NS5A was redistributed from the endoplasmic reticulum to lipid droplets. The NS5A relocalization did not occur in cells treated with other classes of HCV inhibitors, and NS5A-targeting molecules did not cause similar alterations in the localization of other HCV-encoded proteins. Time course analysis of the redistribution of NS5A revealed that the transfer of protein to lipid droplets was concomitant with the onset of inhibition, as judged by the kinetic profiles for these compounds. Furthermore, analysis of the kinetic profile of inhibition for a panel of test molecules permitted the separation of compounds into different kinetic classes based on their modes of action. Results from this approach suggested that NS5A inhibitors perturbed the function of new replication complexes, rather than acting on preformed complexes. Taken together, our data reveal novel biological consequences of NS5A inhibition, which may help enable the development of future assay platforms for the identification of new and/or different NS5A inhibitors.     

New reconstruction of the moroto hominoid snout and a reassessment of its affinities toAfropithecus turkanensis

Two previous reconstructions of the Moroto hominoid palate and face made during the late 1960s suffer from several errors, in particular the angle at which the facial skeleton was hafted onto the palate, and the orientation of the canines, among others. A new reconstruction is based on the discovery that there is a good contact about 1cm logn between the palatal and facial pieces, which reveals that the snout was low and elongated as inAfropithecus turkanensis. Addition of a fragment of the right orbit reveals that the interorbital region was wide as inA. turkanensis. The remaining differences between the skulls from Moroto and Kalodirr are due to five factors:−1) pathology of the Moroto right premaxilla following ante-mortem loss of the right I¹, which led to abnormal enlargement of the right half of the nasal cavity, 2) the incisive foramina of the Moroto palate are damaged, making them appear considerably larger than they were in life, 3) damage to the upper portions of the nasal aperture making it look higher than it would in life, 4) plastic deformation and crushing of the Kalodirr specimen has greatly reduced the width of the palate and has led to the cheek tooth rows converging to the rear, and 5) the slightly larger and ontogenetically older status of the Moroto individual. Resemblances between the Moroto and Kalodirr specimens far outweight the purported or real differences and it is concluded thatMorotopithecus bishopi is a junior subjective synonym ofAfropithecus turkanensis. The sites of Moroto and Kalodirr are unlikely to differ greatly in age (certainly not as much as 4 Ma).     

A new technique for staining mast cells using ferroin

We describe here a new method for specific staining of mast cells using ferroin. Different hamster tissues were fixed in 4% formalin and processed for paraffin embedding. Sections were stained with hematoxylin followed by ferroin acidified with 2.5 N sulfuric acid to pH 4.0. Mast cells stained an intense orange color that contrasted markedly with bluish violet nuclei. High contrast was also observed when ferroin colored sections were counterstained with light green instead of hematoxylin. To evaluate the specificity of the stain, hamster cheek pouch sections were stained with toluidine blue, alcian blue-safranin O, and ferroin. Quantitative evaluation of mast cells stained with the three techniques showed no statistical difference. The simplicity and selectivity of this method is sufficient for image analysis of mast cells.