The needle length of bacterial injectisomes is determined by a molecular ruler

Size determination represents a fundamental requirement for multicomponent biological structures. Some pathogenic bacteria possess a weapon derived from the flagellum. Like the flagellum, this type-III secretion apparatus, called the injectisome, has a transmembrane basal body, but the external component is a needle-like structure instead of a hook and a filament. Here, we provide evidence that the length of this needle is determined by the size of a protein, YscP, acting as a molecular ruler.     

Transient floral change and rapid global warming at the Paleocene-Eocene boundary

Rapid global warming of 5 degrees to 10 degrees C during the Paleocene-Eocene Thermal Maximum (PETM) coincided with major turnover in vertebrate faunas, but previous studies have found little floral change. Plant fossils discovered in Wyoming, United States, show that PETM floras were a mixture of native and migrant lineages and that plant range shifts were large and rapid (occurring within 10,000 years). Floral composition and leaf shape and size suggest that climate warmed by approximately 5 degrees C during the PETM and that precipitation was low early in the event and increased later. Floral response to warming and/or increased atmospheric CO2 during the PETM was comparable in rate and magnitude to that seen in postglacial floras and to the predicted effects of anthropogenic carbon release and climate change on future vegetation.     

Signaling life and death in the thymus: timing is everything

T lymphocytes are generated in the thymus, where developing thymocytes must accept one of two fates: They either differentiate or they die. These fates are chiefly determined by signals that originate from the T cell receptor (TCR), a single receptor complex with a remarkable capacity to decide between distinct cell fates. This review explores TCR signaling in thymocytes and focuses on the kinetic aspects of ligand binding, coreceptor involvement, protein phosphorylation, and mitogen-activated protein kinase (MAPK) activation. Understanding the logic of TCR signaling may eventually explain how thymocytes and T cells distinguish self from nonself, a phenomenon that has fascinated immunologists for 50 years.     

Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast

Aβ (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.     

Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via CD28. Acquisition of CD86 from antigen-presenting cells is stimulated by T cell receptor engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands, accounting for many of the known features of the CD28-CTLA-4 system.     

Denitrification potential of intermittently saturated floodplain soils from a subtropical perennial stream and an ephemeral tributary

Denitrification has the potential to remove excess nitrogen from groundwater passing through riparian buffers, thus improving water quality downstream. In regions with markedly seasonal precipitation, transient stream flow events may be important in saturating adjacent floodplain soils and intermittently providing the anaerobic conditions necessary for denitrification to occur. In two experiments we characterised the denitrification potential of soils from two contrasting floodplains that experience intermittent saturation. We quantified under controlled laboratory conditions: 1) potential rates of denitrification in these soils with depth and over time, for a typical period of saturation; and 2) the influences on rates of nitrate and organic carbon. Treatments differed between experiments, but in each case soil-water slurries were incubated anaerobically with differing amendments of organic carbon and nitrate; denitrification rates were measured at selected time intervals by the acetylene-block technique; and slurry filtrates were analysed for various chemical constituents. In the first experiment (ephemeral tributary), denitrification was evident in soils from both depths (0-0.3 m; 0.3-1.1 m) within hours of saturation. Before Day 2, mean denitrification rates at each depth were generally comparable, irrespective of added substrates; mean rates (Days 0 and 1) were 5.2 ± 0.3 mg N kg dry soil⁻¹ day⁻¹ (0-0.3 m) and 1.6 ± 0.2 mg N kg dry soil⁻¹ day⁻¹ (0.3-1.1 m). Rates generally peaked on Days 2 or 3. The availability of labile organic carbon was a major constraint on denitrification in these soils. Acetate addition greatly increased rates, reaching a maximum in ephemeral floodplain soils of 17.4 ± 1.8 mg N kg dry soil⁻¹ day⁻¹ on Day 2: in one deep-soil treatment (low nitrate) this overcame differences in rates observed with depth when acetate was not added, although the rate increase in the other deep-soil treatment (high nitrate) was significantly less (P ≤ 0.01). Without acetate, peak denitrification rates in this experiment were 6.9 ± 0.4 and 2.8 ± 0.2 mg N kg dry soil⁻¹ day⁻¹ in surface and deep soils, respectively. Differences in rates were observed with depth on all occasions, despite similar initial concentrations of dissolved organic carbon (DOC) at both depths. Levels of substrate addition in the second experiment (perennial stream) more closely reflected natural conditions at the site. Mean denitrification rates were consistently much higher in surface soil (P ≤ 0.001), while the source of water used in the slurries (surface water or groundwater from the site) had little effect on rates at any depth. Mean rates when all treatments retained nitrate were: 4.5 ± 0.3 mg N kg dry soil⁻¹ day⁻¹ (0-0.3 m depth); 0.8 ± 0.3 mg N kg dry soil⁻¹ day⁻¹ (0.3-1.0 m); and 0.6 ± 0.1 mg N kg dry soil⁻¹ day⁻¹ (1.8-3.5 m). For comparable treatments and soil depths, denitrification potentials at both sites were similar, apart from higher initial rates in the ephemeral floodplain soils, probably associated with their higher DOC content and possibly also their history of more frequent saturation. The rapid onset of denitrification and the rates measured in these soils suggest there may be considerable potential for nitrate removal from groundwater in these floodplain environments during relatively short periods of saturation.     

Uterine adenocarcinoma with abdominal metastases in an ovariohysterectomised cat

SURGICAL FINDINGS: an adenocarcinoma of the uterine stump with abdominal metastases is described in a 12.5-year-old incompletely ovariohysterectomised domestic shorthair cat. At the time of presentation, the adenocarcinoma had metastasised to the right perirenal lymph node, the abdominal aorta and the right ureter, resulting in the formation of a large cystic structure. This had compressed and displaced surrounding structures, including the abdominal vena cava and the right kidney, and formed multiple adhesions to the body wall and adjacent abdominal structures. Metastatic extension to the aorta had resulted in its regression into a 2 mm diameter non-pulsatile vessel. PRACTICAL RELEVANCE: only one case of uterine adenocarcinoma has previously been reported in an ovariohysterectomised cat. As such, this represents a very unusual and severe complication following an incomplete ovariohysterectomy. Invasion of the tumour tissue into surrounding structures created further complications.     

Ultrasound findings in horses with severe eyelid swelling, and recognition of acute dacryoadenitis: 10 cases (2004-2010)

Objective To report the sonographic findings, treatment, and outcome of horses with severe eyelid swelling, to describe the sonographic appearance of enlarged lacrimal glands, and to describe the clinical features of acute dacryoadenitis. Materials and methods Medical records of all horses with severe eyelid swelling that underwent an ultrasound evaluation of the globe and periorbital structures from 2004–2010 were examined. Cases were limited to those in which the eyelid swelling was so severe that the globe could not be visualized. Results Ten horses met the criteria for inclusion in the study. All cases were unilateral and acute. Marked enlargement of the lacrimal gland was found in five cases, and supported the diagnosis of acute dacryoadenitis. Eyelid abscessation was found in three horses, accompanied by mild to moderate lacrimal gland enlargement in two of the three. Enlarged lacrimal glands were slightly heterogeneous in appearance and could be differentiated from an abscess by imaging the protrusion of the gland from beneath the supraorbital rim. Only two cases of severe eyelid swelling were soley traumatic. Conclusions Severe eyelid swelling was often associated with dacryoadenitis and/or eyelid abscessation. The detection of marked lacrimal gland enlargement in horses with an acute onset of severe painful eyelid swelling is consistent with a diagnosis of acute dacryoadenitis. Ultrasonographic evaluation of eyelid swelling of any degree is warranted to determine if enlargement of the lacrimal gland, etiology notwithstanding, is an underlying or contributing cause.     

Frequency of equine laminitis: a systematic review with quality appraisal of published evidence

Equine laminitis is a highly debilitating disease of the foot. Despite its perceived importance, epidemiological characteristics are poorly understood and the true frequency of the disease remains unclear. The objective of this study was to retrospectively assess previous research to identify publications which provide the best evidence of the frequency of naturally-occurring equine laminitis. A systematic review of English language publications was conducted using MEDLINE (1950–2010), CAB Direct (1910–2010) and IVIS (1997–2010). Additional publications were included by searching bibliographies. Search terms included laminitis, equine, frequency, prevalence and incidence. Studies that allowed frequency estimations to be made for naturally-occurring equine laminitis were included. Information was extracted using predefined data fields, including 13 study quality indicators.Sixty-nine publications were appraised. Ten were considered to provide the most reliable information, estimating the frequency of equine laminitis ranging from 1.5% to 34%. Previous publications estimating laminitis frequency were generally poor quality. Laminitis frequency varied across publications however the publications included in this review focussed on many of the different underlying laminitis aetiologies and comparison of the frequencies between groups would be inappropriate. High-quality evidence-based studies are needed to estimate the true disease frequency in different equine populations.