Human VPS34 is required for internal vesicle formation within multivesicular endosomes

After internalization from the plasma membrane, activated EGF receptors (EGFRs) are delivered to multivesicular bodies (MVBs). Within MVBs, EGFRs are removed from the perimeter membrane to internal vesicles, thereby being sorted from transferrin receptors, which recycle back to the plasma membrane. The phosphatidylinositol (PI) 3′-kinase inhibitor, wortmannin, inhibits internal vesicle formation within MVBs and causes EGFRs to remain in clusters on the perimeter membrane. Microinjection of isotype-specific inhibitory antibodies demonstrates that the PI 3′-kinase required for internal vesicle formation is hVPS34. In the presence of wortmannin, EGFRs continue to be delivered to lysosomes, showing that their removal from the recycling pathway and their delivery to lysosomes does not depend on inward vesiculation. We showed previously that tyrosine kinase-negative EGFRs fail to accumulate on internal vesicles of MVBs but are recycled rather than delivered to lysosomes. Therefore, we conclude that selection of EGFRs for inclusion on internal vesicles requires tyrosine kinase but not PI 3′-kinase activity, whereas vesicle formation requires PI 3′-kinase activity. Finally, in wortmannin-treated cells there is increased EGF-stimulated tyrosine phosphorylation when EGFRs are retained on the perimeter membrane of MVBs. Therefore, we suggest that inward vesiculation is involved directly with attenuating signal transduction

Bianchi type II,III and V diagonal Einstein metrics re-visited

We present, for both minkowskian and euclidean signatures, short derivations of the diagonal Einstein metrics for Bianchi type II, III and V. For the first two cases we show the integrability of the geodesic flow while for the third case a somewhat unusual bifurcation phenomenon takes place: for minkowskian signature elliptic functions are essential in the metric while for euclidean signature only elementary functions appear

Further results on non-diagonal Bianchi type III vacuum metrics

We present the derivation, for these vacuum metrics, of the Painlev\'e VI equation first obtained by Christodoulakis and Terzis, from the field equations for both minkowskian and euclidean signatures. This allows a complete discussion and the precise connection with some old results due to Kinnersley. The hyperk\"ahler metrics are shown to belong to the Multi-Centre class and for the cases exhibiting an integrable geodesic flow the relevant Killing tensors are given. We conclude by the proof that for the Bianchi B family, excluding type III, there are no hyperk\"ahler metrics.Comment: 21 pages, no figure

The sensorium at work: the sensory phenomenology of the working body

The sociology of the body and the sociology of work and occupations have both neglected to some extent the study of the ‘working body’ in paid employment, particularly with regard to empirical research into the sensory aspects of working practices. This gap is perhaps surprising given how strongly the sensory dimension features in much of working life. This article is very much a first step in calling for a more phenomenological, embodied and ‘fleshy’ perspective on the body in employment, and examines some of the theoretical and conceptual resources available to researchers wishing to focus on the lived working-body experiences of the sensorium. We also consider some possible representational forms for a more evocative, phenomenologically-inspired portrayal of sensory, lived-working-body experiences, and offer suggestions for future avenues of research

True substrates: The exceptional resolution and unexceptional preservation of deep time snapshots on bedding surfaces

Abstract: Rock outcrops of the sedimentary–stratigraphic record often reveal bedding planes that can be considered to be true substrates: preserved surfaces that demonstrably existed at the sediment–water or sediment–air interface at the time of deposition. These surfaces have high value as repositories of palaeoenvironmental information, revealing fossilized snapshots of microscale topography from deep time. Some true substrates are notable for their sedimentary, palaeontological and ichnological signatures that provide windows into key intervals of Earth history, but countless others occur routinely throughout the sedimentary–stratigraphic record. They frequently reveal patterns that are strikingly familiar from modern sedimentary environments, such as ripple marks, animal trackways, raindrop impressions or mudcracks: all phenomena that are apparently ephemeral in modern settings, and which form on recognizably human timescales. This paper sets out to explain why these short‐term, transient, small‐scale features are counter‐intuitively abundant within a 3.8 billion year‐long sedimentary–stratigraphic record that is known to be inherently time‐incomplete. True substrates are fundamentally related to a state of stasis in ancient sedimentation systems, and distinguishable from other types of bedding surfaces that formed from a dominance of states of deposition or erosion. Stasis is shown to play a key role in both their formation and preservation, rendering them faithful and valuable archives of palaeoenvironmental and temporal information. Further, the intersection between the time–length scale of their formative processes and outcrop expressions can be used to explain why they are so frequently encountered in outcrop investigations. Explaining true substrates as inevitable and unexceptional by‐products of the accrual of the sedimentary–stratigraphic record should shift perspectives on what can be understood about Earth history from field studies of the sedimentary–stratigraphic record. They should be recognized as providing high‐definition information about the mundane day to day operation of ancient environments, and critically assuage the argument that the incomplete sedimentary–stratigraphic record is unrepresentative of the geological past

Effects of balloon occlusion during percutaneous coronary intervention on circulating Ischemia Modified Albumin and transmyocardial lactate extraction

Studies have shown that human albumin undergoes a considerable reduction in its capacity to bind exogenous cobalt (Ischemia Modified Albumin (IMA); Ischemia Technologies, Denver, Colorado, USA), as measured by the albumin cobalt binding test, when exposed to an ischaemic insult. We have recently observed that plasma IMA levels increase soon after transient balloon inflation during percutaneous coronary intervention (PCI), even in the absence of considerable elevations of cardiac troponin.1 Higher IMA levels have also been reported in patients with acute coronary syndrome attending the emergency department with recent‐onset chest pain.2 At present however, no data exist regarding the relationship between IMA and an accepted gold standard for myocardial ischaemia—that is, myocardial lactate extraction.3 We therefore sought to assess whether increased IMA plasma levels documented in patients after PCI correlate with an increased production of lactate by the myocardium

The effects of straw disposal and depth of cultivation on the growth, nutrient uptake and yield of winter wheat on a clay and a silt soil

Experiments were conducted for one year on two different soil types. On a clay soil straw was either (a) burnt, (b) baled leaving the stubble, or (c) chopped and spread. The soil was tine cultivated to depths of 5, 10 or 15 cm or ploughed to 20 or 30 cm before winter wheat was sown conventionally. In addition, a direct-drilled crop was sown after each straw treatment. On a silt loam soil the direct-drilled, tine cultivated to 15 cm and ploughed to 30 cm treatments following burning or chopping and spreading straw were repeated. Tine cultivation incorporated less straw than ploughing, decreased plant establishment and early growth but did not decrease yield. Direct-drilling through chopped straw decreased yield on the silt loam but not on the clay soil. Short straw (< 5 cm) was easier to incorporate than longer straw. Ploughing was the most efficient method of straw incorporation because it inverts soil. Early effects on crop growth and nutrient uptake following straw incorporation were transient and associated with large amounts of straw in the seeded layer of soil

Maternal smoking during pregnancy specifically reduces human fetal desert hedgehog gene expression during testis development

&lt;br&gt;Context: Maternal cigarette smoking during gestation increases cryptorchidism and hypospadias and reduces testis size and fertility in sons by unknown mechanisms.&lt;/br&gt; &lt;br&gt;Objective: The objective of the study was to determine whether maternal smoking is linked with changes in male human fetal endocrinology, testis gene expression, and liver concentrations of cigarette smoke chemicals.&lt;/br&gt; &lt;br&gt;Design: This was an observational study of the male fetus, comparing pregnancies during which the mothers either did or did not smoke.&lt;/br&gt; &lt;br&gt;Setting: The study was conducted at the universities of Aberdeen, Glasgow, and Nottingham and Macaulay Institute (Aberdeen).&lt;/br&gt; &lt;br&gt;Patients/Participants: Testes, blood, and livers were collected from 69 morphologically normal human male fetuses of women undergoing elective termination of normal second-trimester pregnancies.&lt;/br&gt; &lt;br&gt;Main Outcome Measures: Testosterone, human chorionic gonadotropin, LH, and cotinine; expression of 30 reproductive/developmental genes; liver concentrations of 16 polycyclic aromatic hydrocarbons; and Leydig, Sertoli. and germ cell numbers were determined.&lt;/br&gt; &lt;br&gt;Results: There were no significant differences in fetal size, testis weight, cell numbers, seminiferous tubule diameter, or circulating LH and testosterone. Fetuses from smoking mothers had smoking range cotinine levels and liver concentrations of polycyclic aromatic hydrocarbons that were significant predictors of maternal smoking (P &#60; 0.001). Only the Sertoli cell-specific gene, desert hedgehog (DHH), was significantly altered by maternal smoking (reduced 1.8-fold, P = 0.013).&lt;/br&gt; &lt;br&gt;Conclusions: The consequences of reduced DHH signaling in men and mice are consistent with epidemiology for effects of gestational maternal smoking on sons. Given the absence of other observed effects of maternal smoking, we concluded that reduced DHH is part of a mechanism linking maternal gestational smoking with impaired reproductive development in male offspring.&lt;/br&gt