bluuebunny/crossref_metadata_2025 huggingface dataset:
HPat provides a link between deadenylation and decapping in metazoa
Authors: Haas Gabrielle , Braun Joerg E. , Igreja Cátia , Tritschler Felix , Nishihara Tadashi , Izaurralde Elisa
Published: April 2010

Decapping of eukaryotic messenger RNAs (mRNAs) occurs after they have undergone deadenylation, but how these processes are coordinated is poorly understood. In this study, we report that Drosophila melanogaster HPat (homologue of Pat1), a conserved decapping activator, interacts with additional decapping factors (e.g., Me31B, the LSm1–7 complex, and the decapping enzyme DCP2) and with components of the CCR4–NOT deadenylase complex. Accordingly, HPat triggers deadenylation and decapping when artificially tethered to an mRNA reporter. These activities reside, unexpectedly, in a proline-rich region. However, this region alone cannot restore decapping in cells depleted of endogenous HPat but also requires the middle (Mid) and the very C-terminal domains of HPat. We further show that the Mid and C-terminal domains mediate HPat recruitment to target mRNAs. Our results reveal an unprecedented role for the proline-rich region and the C-terminal domain of metazoan HPat in mRNA decapping and suggest that HPat is a component of the cellular mechanism that couples decapping to deadenylation in vivo.
Rho1 regulates apoptosis via activation of the JNK signaling pathway at the plasma membrane
Authors: Neisch Amanda L. , Speck Olga , Stronach Beth , Fehon Richard G.
Published: April 2010

Precisely controlled growth and morphogenesis of developing epithelial tissues require coordination of multiple factors, including proliferation, adhesion, cell shape, and apoptosis. RhoA, a small GTPase, is known to control epithelial morphogenesis and integrity through its ability to regulate the cytoskeleton. In this study, we examine a less well-characterized RhoA function in cell survival. We demonstrate that the Drosophila melanogaster RhoA, Rho1, promotes apoptosis independently of Rho kinase through its effects on c-Jun NH2-terminal kinase (JNK) signaling. In addition, Rho1 forms a complex with Slipper (Slpr), an upstream activator of the JNK pathway. Loss of Moesin (Moe), an upstream regulator of Rho1 activity, results in increased levels of Rho1 at the plasma membrane and cortical accumulation of Slpr. Together, these results suggest that Rho1 functions at the cell cortex to regulate JNK activity and implicate Rho1 and Moe in epithelial cell survival.
αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration
Authors: Worth Daniel C. , Hodivala-Dilke Kairbaan , Robinson Stephen D. , King Samantha J. , Morton Penny E. , Gertler Frank B. , Humphries Martin J. , Parsons Maddy
Published: April 2010

Integrins are fundamental to the control of protrusion and motility in adherent cells. However, the mechanisms by which specific members of this receptor family cooperate in signaling to cytoskeletal and adhesion dynamics are poorly understood. Here, we show that the loss of β3 integrin in fibroblasts results in enhanced focal adhesion turnover and migration speed but impaired directional motility on both 2D and 3D matrices. These motility defects are coupled with an increased rate of actin-based protrusion. Analysis of downstream signaling events reveals that loss of β3 integrin results in a loss of protein kinase A–dependent phosphorylation of the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP). Dephosphorylated VASP in β3-null cells is preferentially associated with Rap1-GTP–interacting adaptor molecule (RIAM) both in vitro and in vivo, which leads to enhanced formation of a VASP–RIAM complex at focal adhesions and subsequent increased binding of talin to β1 integrin. These data demonstrate a novel mechanism by which αvβ3 integrin acts to locally suppress β1 integrin activation and regulate protrusion, adhesion dynamics, and persistent migration.
Cyclin B–Cdk1 activates its own pump to get into the nucleus
Authors: Lindqvist Arne
Published: April 2010

The transition to mitosis requires extensive nuclear and cytoplasmic rearrangements that must be spatially and temporally coordinated. In this issue, Gavet and Pines (2010a. J. Cell Biol. doi:10.1083/jcb.200909144) report on a simple yet elegant mechanism as to how this is achieved. By monitoring the activity of cyclin B–Cdk1 in real time, the authors show that concomitant with its activation in the cytoplasm, the kinase complex is rapidly imported into the nucleus by modifying the activity of the nucleocytoplasmic transport machinery. Thus, cyclin B–Cdk1 activates its own pump to get into the nucleus.
Universal Methicillin-ResistantStaphylococcus aureus(MRSA) Surveillance for Adults at Hospital Admission: An Economic Model and Analysis
Authors: Lee Bruce Y. , Bailey Rachel R. , Smith Kenneth J. , Muder Robert R. , Strotmeyer Elsa S. , Lewis G. Jonathan , Ufberg Paul J. , Song Yeohan , Harrison Lee H.
Published: April 2010

Background.

Methicillin-resistantStaphylococcus aureus(MRSA) transmission and infections are a continuing problem in hospitals. Although some have recommended universal surveillance for MRSA at hospital admission to identify and to isolate MRSA-colonized patients, there is a need for formal economic studies to determine the cost-effectiveness of such a strategy.

Methods.

We developed a stochastic computer simulation model to determine the potential economic impact of performing MRSA surveillance (ie, single culture of an anterior nares specimen) for all hospital admissions at different MRSA prevalences and basic reproductive rate thresholds from the societal and third party-payor perspectives. Patients with positive surveillance culture results were placed under isolation precautions to prevent transmission by way of respiratory droplets. MRSA-colonized patients who were not isolated could transmit MRSA to other hospital patients.

Results.

The performance of universal MRSA surveillance was cost-effective (defined as an incremental cost-effectiveness ratio of less than $50,000 per quality-adjusted life-year) when the basic reproductive rate was 0.25 or greater and the prevalence was 1% or greater. In fact, surveillance was the dominant strategy when the basic reproductive rate was 1.5 or greater and the prevalence was 15% or greater, the basic reproductive rate was 2.0 or greater and the prevalence was 10% or greater, and the basic reproductive rate was 2.5 or greater and the prevalence was 5% or greater.

Conclusions.

Universal MRSA surveillance of adults at hospital admission appears to be cost-effective at a wide range of prevalence and basic reproductive rate values. Individual hospitals and healthcare systems could compare their prevailing conditions (eg, the prevalence of MRSA colonization and MRSA transmission dynamics) with the benchmarks in our model to help determine their optimal local strategies.
Social Software and Digital Competences
Authors: Sandars John
Published: April 2010

The use of the Internet and technology has become an integral part of daily life. An important aspect has been the rise of social software and a wide variety of services, from instant messaging to social networking, are now used by millions of people across the world. The opportunity to use these services is no longer restricted to a personal computer because most are also easily accessible by mobile phones. The challenge is how to effectively use what is essentially a social and leisure phenomenon as something that can add value to teaching and enhance learning. New and innovative approaches to education are required but effectively responding to this challenge requires the development of a new range of so-called digital competences.
Childhood Constipation
Authors: Watson Laura
Published: April 2010

Constipation in childhood is a common problem that is frequently seen in general practice. Constipation can be defined as an infrequent passage of stool or difficulty passing stools. The term also encompasses distress on defecation and a feeling of incomplete evacuation. The aims of this article are to provide an overview of how to approach constipation in general practice. This approach will include how to diagnose constipation, consideration of predisposing factors, treatment options and when to refer.
Bowel Obstruction
Authors: Wiggins Tom , Stephenson James A. , Al-Taan Omer , Metcalfe Matthew S. , Dennison Ashley R.
Published: April 2010

Bowel obstruction is a common surgical emergency. It can affect the small or large bowel and there are a number of possible aetiologies. Management requires prompt identification and referral to secondary care for further investigation and possible surgical intervention. Early diagnosis and management planning are the key to reducing morbidity and mortality associated with bowel obstruction from any cause.
An Audit of Bone Densitometry Measurement in Patients with Coeliac Disease
Authors: Edwards John
Published: April 2010

There is a well documented association between coeliac disease and reduced bone mineral density (BMD). Osteopenia and osteoporosis are both preventable and treatable. There are clear clinical recommendations available for measuring BMD in subgroups of patients with coeliac disease. However, it is suspected that within the practice population these standards are not being achieved. This suspicion is based on routine clinical encounters with patients with coeliac disease.
Malaria
Authors: Garland Melissa
Published: April 2010

Malaria is a preventable and treatable disease that can be life threatening and difficult to diagnose. It is the most commonly imported tropical disease in the UK. From 2000 to 2008, there were 85 deaths in the UK from malaria, an average of nine per year. It is essential that GPs are able to identify those at high risk and act accordingly to prevent fatalities.
Illness in Returning Travellers
Authors: Jones Nick , Simon Chantal
Published: April 2010

With cheap airfares, international travel has become commonplace. In 2007, around 70 million trips abroad were made by UK residents compared to 30 million in 1987. Around 1 in 10 travellers seek medical attention for symptoms that they have developed abroad after visiting the developing world, either while still abroad or on their return to the UK. This article aims to provide the GP with a strategy to deal with such patients presenting to primary care.
Constipation in Adults
Authors: Khan Farooq , Simon Chantal
Published: April 2010

Constipation affects about 15–20% of the population in the UK. It tends to cause problems at the extremes of age and women are more commonly affected than men. Constipation is associated with irritable bowel syndrome (IBS) in 59%, pelvic floor dysfunction in 29% and slow transit in 13%. Many people manage their constipation themselves with diet or over-the-counter medication. This article aims to provide a strategy for GPs to manage those with more severe symptoms who present to general practice.
Response of faults to climate-driven changes in ice and water volumes on Earth’s surface
Authors: Hampel Andrea , Hetzel Ralf , Maniatis Georgios
Published: April 2010

Numerical models including one or more faults in a rheologically stratified lithosphere show that climate-induced variations in ice and water volumes on Earth’s surface considerably affect the slip evolution of both thrust and normal faults. In general, the slip rate and hence the seismicity of a fault decreases during loading and increases during unloading. Here, we present several case studies to show that a postglacial slip rate increase occurred on faults worldwide in regions where ice caps and lakes decayed at the end of the last glaciation. Of note is that the postglacial amplification of seismicity was not restricted to the areas beneath the large Laurentide and Fennoscandian ice sheets but also occurred in regions affected by smaller ice caps or lakes, e.g. the Basin-and-Range Province. Our results do not only have important consequences for the interpretation of palaeoseismological records from faults in these regions but also for the evaluation of the future seismicity in regions currently affected by deglaciation like Greenland and Antarctica: shrinkage of the modern ice sheets owing to global warming may ultimately lead to an increase in earthquake frequency in these regions.
Climate effects on volcanism: influence on magmatic systems of loading and unloading from ice mass variations, with examples from Iceland
Authors: Sigmundsson Freysteinn , Pinel Virginie , Lund Björn , Albino Fabien , Pagli Carolina , Geirsson Halldór , Sturkell Erik
Published: April 2010

Pressure influences both magma production and the failure of magma chambers. Changes in pressure interact with the local tectonic settings and can affect magmatic activity. Present-day reduction in ice load on subglacial volcanoes due to global warming is modifying pressure conditions in magmatic systems. The large pulse in volcanic production at the end of the last glaciation in Iceland suggests a link between unloading and volcanism, and models of that process can help to evaluate future scenarios. A viscoelastic model of glacio-isostatic adjustment that considers melt generation demonstrates how surface unloading may lead to a pulse in magmatic activity. Iceland’s ice caps have been thinning since 1890 and glacial rebound at rates exceeding 20 mm yr−1is ongoing. Modelling predicts a significant amount of ‘additional’ magma generation under Iceland due to ice retreat. The unloading also influences stress conditions in shallow magma chambers, modifying their failure conditions in a manner that depends critically on ice retreat, the shape and depth of magma chambers as well as the compressibility of the magma. An annual cycle of land elevation in Iceland, due to seasonal variation of ice mass, indicates an annual modulation of failure conditions in subglacial magma chambers.
Statistical analysis of the El Niño–Southern Oscillation and sea-floor seismicity in the eastern tropical Pacific
Authors: Guillas Serge , Day Simon J. , McGuire B.
Published: April 2010

We present statistical evidence for a temporal link between variations in the El Niño–Southern Oscillation (ENSO) and the occurrence of earthquakes on the East Pacific Rise (EPR). We adopt a zero-inflated Poisson regression model to represent the relationship between the number of earthquakes in the Easter microplate on the EPR and ENSO (expressed using the southern oscillation index (SOI) for east Pacific sea-level pressure anomalies) from February 1973 to February 2009. We also examine the relationship between the numbers of earthquakes and sea levels, as retrieved by Topex/Poseidon from October 1992 to July 2002. We observe a significant (95% confidence level) positive influence of SOI on seismicity: positive SOI values trigger more earthquakes over the following 2 to 6 months than negative SOI values. There is a significant negative influence of absolute sea levels on seismicity (at 6 months lag). We propose that increased seismicity is associated with ENSO-driven sea-surface gradients (rising from east to west) in the equatorial Pacific, leading to a reduction in ocean-bottom pressure over the EPR by a few kilopascal. This relationship is opposite to reservoir-triggered seismicity and suggests that EPR fault activity may be triggered by plate flexure associated with the reduced pressure.
Climate forcing of volcano lateral collapse: evidence from Mount Etna, Sicily
Authors: Deeming K. R. , McGuire B. , Harrop P.
Published: April 2010

In this study, we present evidence for early Holocene climatic conditions providing circumstances favourable to major lateral collapse at Mount Etna, Sicily. The volcano’s most notable topographic feature is the Valle del Bove, a 5×8 km cliff-bounded amphitheatre excavated from the eastern flank of the volcano. Its origin due to prehistoric lateral collapse is corroborated by stürtzstrom deposits adjacent to the amphitheatre’s downslope outlet, but the age, nature and cause of amphitheatre excavation remain matters for debate. Cosmogenic
3
He exposure ages determined for eroded surfaces within an abandoned watershed flanking the Valle del Bove support channel abandonment
ca
7.5 ka BP, as a consequence of its excavation in a catastrophic collapse event. Watershed development was largely dictated by pluvial conditions during the early Holocene, which are also implicated in slope failure. A viable trigger is magma emplacement into rift zones in the eastern flank of a water-saturated edifice, leading to the development of excess pore pressures, consequent reduction in sliding resistance, detachment and collapse. Such a mechanism is presented as one potential driver of future lateral collapse in volcanic landscapes forecast to experience increased precipitation or melting of ice cover as a consequence of anthropogenic warming.
Gas hydrates: past and future geohazard?
Authors: Maslin Mark , Owen Matthew , Betts Richard , Day Simon , Dunkley Jones Tom , Ridgwell Andrew
Published: April 2010

Gas hydrates are ice-like deposits containing a mixture of water and gas; the most common gas is methane. Gas hydrates are stable under high pressures and relatively low temperatures and are found underneath the oceans and in permafrost regions. Estimates range from 500 to 10 000 giga tonnes of carbon (best current estimate 1600–2000 GtC) stored in ocean sediments and 400 GtC in Arctic permafrost. Gas hydrates may pose a serious geohazard in the near future owing to the adverse effects of global warming on the stability of gas hydrate deposits both in ocean sediments and in permafrost. It is still unknown whether future ocean warming could lead to significant methane release, as thermal penetration of marine sediments to the clathrate–gas interface could be slow enough to allow a new equilibrium to occur without any gas escaping. Even if methane gas does escape, it is still unclear how much of this could be oxidized in the overlying ocean. Models of the global inventory of hydrates and trapped methane bubbles suggest that a global 3°C warming could release between 35 and 940 GtC, which could add up to an additional 0.5°C to global warming. The destabilization of gas hydrate reserves in permafrost areas is more certain as climate models predict that high-latitude regions will be disproportionately affected by global warming with temperature increases of over 12°C predicted for much of North America and Northern Asia. Our current estimates of gas hydrate storage in the Arctic region are, however, extremely poor and non-existent for Antarctica. The shrinking of both the Greenland and Antarctic ice sheets in response to regional warming may also lead to destabilization of gas hydrates. As ice sheets shrink, the weight removed allows the coastal region and adjacent continental slope to rise through isostacy. This removal of hydrostatic pressure could destabilize gas hydrates, leading to massive slope failure, and may increase the risk of tsunamis.
Submarine mass failures as tsunami sources: their climate control
Authors: Tappin D. R.
Published: April 2010

Recent research on submarine mass failures (SMFs) shows that they are a source of hazardous tsunamis, with the tsunami magnitude mainly dependent on water depth of failure, SMF volume and failure mechanism, cohesive slump or fragmental landslide. A major control on the mechanism of SMFs is the sediment type, together with its post-depositional alteration. The type of sediment, fine- or coarse-grained, its rate of deposition together with post-depositional processes may all be influenced by climate. Post-depositional processes, termed sediment ‘preconditioning’, are known to promote instability and failure. Climate may also control the triggering of SMFs, for example through earthquake loading or cyclic loading from storm waves or tides. Instantaneous triggering by other mechanisms such as fluid overpressuring and hydrate instability is controversial, but is here considered unlikely. However, these mechanisms are known to promote sediment instability. SMFs occur in numerous environments, including the open continental shelf, submarine canyon/fan systems, fjords, active river deltas and convergent margins. In all these environments there is a latitudinal variation in the scale of SMFs. The database is limited, but the greatest climate influence appears to be in high latitudes where glacial/interglacial cyclicity has considerable control on sedimentation, preconditioning and triggering. Consideration of the different types of SMFs in the context of their climate controls provides additional insight into their potential hazard in sourcing tsunamis. For example, in the Atlantic, where SMFs are common, the tsunami hazard under the present-day climate may not be as great as their common occurrence suggests.
Androgens and spermatogenesis: lessons from transgenic mouse models
Authors: Verhoeven Guido , Willems Ariane , Denolet Evi , Swinnen Johannes V. , De Gendt Karel
Published: April 2010

Transgenic mouse models have contributed considerably to our understanding of the cellular and molecular mechanisms by which androgens control spermatogenesis. Cell-selective ablation of the androgen receptor (AR) in Sertoli cells (SC) results in a complete block in meiosis and unambiguously identifies the SC as the main cellular mediator of the effects of androgens on spermatogenesis. This conclusion is corroborated by similar knockouts in other potential testicular target cells. Mutations resulting in diminished expression of the AR or in alleles with increased length of the CAG repeat mimick specific human forms of disturbed fertility that are not accompanied by defects in male sexual development. Transcriptional profiling studies in mice with cell-selective and general knockouts of the AR, searching for androgen-regulated genes relevant to the control of spermatogenesis, have identified many candidate target genes. However, with the exception ofRhox5, the identified subsets of genes show little overlap. Genes related to tubular restructuring, cell junction dynamics, the cytoskeleton, solute transportation and vitamin A metabolism are prominently present. Further research will be needed to decide which of these genes are physiologically relevant and to identify genes that can be used as diagnostic tools or targets to modulate the effects of androgens in spermatogenesis.
Transcription and post-transcriptional regulation of spermatogenesis
Authors: Bettegowda Anilkumar , Wilkinson Miles F.
Published: April 2010

Spermatogenesis in mammals is achieved by multiple players that pursue a common goal of generating mature spermatozoa. The developmental processes acting on male germ cells that culminate in the production of the functional spermatozoa are regulated at both the transcription and post-transcriptional levels. This review addresses recent progress towards understanding such regulatory mechanisms and identifies future challenges to be addressed in this field. We focus on transcription factors, chromatin-associated factors and RNA-binding proteins necessary for spermatogenesis and/or sperm maturation. Understanding the molecular mechanisms that govern spermatogenesis has enormous implications for new contraceptive approaches and treatments for infertility.
Oestrogens and spermatogenesis
Authors: Carreau Serge , Hess Rex A.
Published: April 2010

The role of oestrogens in male reproductive tract physiology has for a long time been a subject of debate. The testis produces significant amounts of oestrogenic hormones, via aromatase, and oestrogen receptors (ERs)α (ESR1) and ERβ (ESR2) are selectively expressed in cells of the testis as well as the epididymal epithelium, depending upon species. This review summarizes the current knowledge concerning the presence and activity of aromatase and ERs in testis and sperm and the potential roles that oestrogens may have in mammalian spermatogenesis. Data show that physiology of the male gonad is in part under the control of a balance of androgens and oestrogens, with aromatase serving as a modulator.
Sertoli–germ cell junctions in the testis: a review of recent data
Authors: Kopera Ilona A. , Bilinska Barbara , Cheng C. Yan , Mruk Dolores D.
Published: April 2010

Spermatogenesis is a process that involves an array of cellular and biochemical events, collectively culminating in the formation of haploid spermatids from diploid precursor cells known as spermatogonia. As germ cells differentiate from spermatogonia into elongated spermatids, they also progressively migrate across the entire length of the seminiferous epithelium until they reach the luminal edge in anticipation of spermiation at late stage VIII of spermatogenesis. At the same time, these germ cells must maintain stable attachment with Sertoli cells via testis-unique intermediate filament- (i.e. desmosome-like junctions) and actin- (i.e. ectoplasmic specializations, ESs) based cell junctions to prevent sloughing of immature germ cells from the seminiferous epithelium, which may result in infertility. In essence, both desmosome-like junctions and basal ESs are known to coexist between Sertoli cells at the level of the blood–testis barrier where they cofunction with the well-studied tight junction in maintaining the immunological barrier. However, the type of anchoring device that is present between Sertoli and germ cells depends on the developmental stage of the germ cell, i.e. desmosome-like junctions are present between Sertoli and germ cells up to, but not including, step 8 spermatids after which this junction type is replaced by the apical ES. While little is known about the biology of the desmosome-like junction in the testis, we have a relatively good understanding of the molecular architecture and the regulation of the ES. Here, we discuss recent findings relating to these two junction types in the testis, highlighting prospective areas that should be investigated in future studies.
Regulating mitosis and meiosis in the male germ line: critical functions for cyclins
Authors: Wolgemuth Debra J. , Roberts Shelby S.
Published: April 2010

Key components of the cell cycle machinery are the regulatory subunits, the cyclins, and their catalytic partners the cyclin-dependent kinases. Regulating the cell cycle in the male germ line cells represents unique challenges for this machinery given the constant renewal of gametes throughout the reproductive lifespan and the induction of the unique process of meiosis, a highly specialized kind of cell division. With challenges come opportunities to the critical eye, recognizing that understanding these specialized modes of regulation will provide considerable insight into both normal differentiation as well as disease conditions, including infertility and oncogenesis.
Cytoskeletal dynamics and spermatogenesis
Authors: Lie Pearl P. Y. , Mruk Dolores D. , Lee Will M. , Cheng C. Yan
Published: April 2010

Different cellular events occur during spermatogenesis, and these include (i) mitosis for self-renewal of spermatogonia, (ii) differentiation of type A spermatogonia into type B and commitment of type B spermatogonia to develop into preleptotene primary spermatocytes, (iii) transit of preleptotene/leptotene spermatocytes across the blood–testis barrier in coordination with germ cell cycle progression and meiosis, (iv) spermiogenesis and spermiation. These events also associate with extensive changes in cell shape and size, and germ cell movement. The cytoskeleton, which comprises actin, microtubules and intermediate filaments, is believed to function in these cellular events. However, few studies have been conducted by investigators in the past decades to unfold the role of the cytoskeleton during spermatogenesis. This review summarizes recent advances in the field relating to cytoskeletal dynamics in the testis, and highlights areas of research that require additional emphasis so that new approaches for male contraception, as well as therapeutic approaches to alleviate environmental toxicant-induced reproductive dysfunction in men, can possibly be developed.
Testicular postgenomics: targeting the regulation of spermatogenesis
Authors: Calvel Pierre , Rolland Antoine D. , Jégou Bernard , Pineau Charles
Published: April 2010

Sperm are, arguably, the most differentiated cells produced within the body of any given species. This is owing to the fact that spermatogenesis is an intricate and highly specialized process evolved to suit the individual particularities of each sexual species. Despite a vast diversity in method, the aim of spermatogenesis is always the same, the idealized transmission of genetic patrimony. Towards this goal certain requirements must always be met, such as a relative twofold reduction in ploidy, repackaging of the chromatin for transport and specialized enhancements for cell motility, recognition and fusion. In the past 20 years, the study of molecular networks coordinating male germ cell development, particularly in mammals, has become more and more facilitated thanks to large-scale analyses of genome expression. Such postgenomic endeavors have generated landscapes of data for both fundamental and clinical reproductive biology. Continuous, large-scale integration analyses of these datasets are undertaken which provide access to very precise information on a myriad of biomolecules. This review presents commonly used transcriptomic and proteomic workflows applied to various testicular germ cell studies. We will also provide a general overview of the technical possibilities available to reproductive genomic biologists, noting the advantages and drawbacks of each technique.
Tight junctions in the testis: new perspectives
Authors: Mruk Dolores D. , Cheng C. Y.
Published: April 2010

In the testis, tight junctions (TJs) are found between adjacent Sertoli cells at the level of the blood–testis barrier (BTB) where they coexist with basal ectoplasmic specializations and desmosome-gap junctions. The BTB physically divides the seminiferous epithelium into two distinct compartments: a basal compartment where spermatogonia and early spermatocytes are found, and an adluminal compartment where more developed germ cells are sequestered from the systemic circulation. In order for germ cells (i.e. preleptotene spermatocytes) to enter the adluminal compartment, they must cross the BTB, a cellular event requiring the participation of several molecules and signalling pathways. Still, it is not completely understood how preleptotene spermatocytes traverse the BTB at stage VIII of the seminiferous epithelial cycle. In this review, we discuss largely how TJ proteins are exploited by viruses and cancer cells to cross endothelial and epithelial cells. We also discuss how this information may apply to future studies investigating the movement of preleptotene spermatocytes across the BTB.
The biology of spermatogenesis: the past, present and future
Authors: Cheng C. Yan , Mruk Dolores D.
Published: April 2010

The physiological function of spermatogenesis in
Caenorhabditis elegans
,
Drosophila melanogaster
and mammals is to produce spermatozoa (1n, haploid) that contain only half of the genetic material of spermatogonia (2n, diploid). This half number of chromosomes from a spermatozoon will then be reconstituted to become a diploid cell upon fertilization with an egg, which is also haploid. Thus, genetic information from two parental individuals can be passed onto their offspring. Spermatogenesis takes place in the seminiferous epithelium of the seminiferous tubule, the functional unit of the mammalian testis. In mammals, particularly in rodents, the fascinating morphological changes that occur during spermatogenesis involving cellular differentiation and transformation, mitosis, meiosis, germ cell movement, spermiogenesis and spermiation have been well documented from the 1950s through the 1980s. During this time, however, the regulation of, as well as the biochemical and molecular mechanisms underlying these diverse cellular events occurring throughout spermatogenesis, have remained largely unexplored. In the past two decades, important advancements have been made using new biochemical, cell and molecular biology techniques to understand how different genes, proteins and signalling pathways regulate various aspects of spermatogenesis. These include studies on the differentiation of spermatogonia from gonocytes; regulation of spermatogonial stem cells; regulation of spermatogonial mitosis; regulation of meiosis, spermiogenesis and spermiation; role of hormones (e.g. oestrogens, androgens) in spermatogenesis; transcriptional regulation of spermatogenesis; regulation of apoptosis; cell–cell interactions; and the biology of junction dynamics during spermatogenesis. The impact of environmental toxicants on spermatogenesis has also become an urgent issue in the field in light of declining fertility levels in males. Many of these studies have helped investigators to understand important similarities, differences and evolutionary relationships between
C. elegans
,
D. melanogaster
and mammals relating to spermatogenesis. In this Special Issue of the
Philosophical Transactions of the Royal Society B: Biological Sciences
, we have covered many of these areas, and in this
Introduction
, we highlight the topic of spermatogenesis by examining its past, present and future.
Claudin and occludin expression and function in the seminiferous epithelium
Authors: Morrow Carla M. K. , Mruk Dolores , Cheng C. Yan , Hess Rex A.
Published: April 2010

Integral membrane proteins that contribute to function of the blood–testes barrier (BTB) in mice include claudins 3, 5 and 11 and occludin. Although claudin 11 is expressed throughout all stages of the seminiferous epithelial cycle, claudins 3 and 5 have specific expression at stage VIII. These differences in protein expression suggest that the interactions among, and functions of, these integral membrane proteins may shift over the course of the seminiferous epithelial cycle. Also, differences in expression among rodent species and men may make interpretation of studies across species challenging. This review will discuss the characteristics of claudins and occludin; the expression, regulation and function of these integral membrane proteins in the seminiferous epithelium; and how these properties relate to the unique features of BTB.
Epigenetic control of plant immunity
Authors: ALVAREZ MARÍA E. , NOTA FLORENCIA , CAMBIAGNO DAMIÁN A.
Published: April 2010

In eukaryotic genomes, gene expression and DNA recombination are affected by structural chromatin traits. Chromatin structure is shaped by the activity of enzymes that either introduce covalent modifications in DNA and histone proteins or use energy from ATP to disrupt histone–DNA interactions. The genomic ‘marks’ that are generated by covalent modifications of histones and DNA, or by the deposition of histone variants, are susceptible to being altered in response to stress. Recent evidence has suggested that proteins generating these epigenetic marks play crucial roles in the defence against pathogens. Histone deacetylases are involved in the activation of jasmonic acid‐ and ethylene‐sensitive defence mechanisms. ATP‐dependent chromatin remodellers mediate the constitutive repression of the salicylic acid‐dependent pathway, whereas histone methylation at the WRKY70 gene promoter affects the activation of this pathway. Interestingly, bacterial‐infected tissues show a net reduction in DNA methylation, which may affect the disease resistance genes responsible for the surveillance against pathogens. As some epigenetic marks can be erased or maintained and transmitted to offspring, epigenetic mechanisms may provide plasticity for the dynamic control of emerging pathogens without the generation of genomic lesions.
Experimental global food reduction raises resource acquisition costs of brood care helpers and reduces their helping effort
Authors: Bruintjes Rick , Hekman Renske , Taborsky Michael
Published: April 2010

1. Ecological conditions and constraints are considered to be important for the evolution of cooperative breeding. However, the importance of the costs of resource acquisition to the decision of subordinates to stay or leave and to help or not have been hardly studied experimentally. Here we reduced the overall food availability (zooplankton) for experimental populations of the cooperatively breeding cichlid fish Neolamprologus pulcher in the field and measured effects on subordinates’ spacing, dispersal, interactions, and helping behaviour.

2. When plankton availability was reduced, all helpers increased feeding rate and moved further away from shelter. Helping correlated negatively with feeding, which suggests a trade‐off between foraging effort and cooperation. All group members attacked experimentally presented egg predators later in the food reduction treatment and small helpers in particular decreased their defence effort against them. Furthermore, all subordinates tended to perform less work when food was reduced.

3. This is the first study where food availability was generally reduced in the environment of a cooperative breeder, without affecting the resource distribution between territories. Thereby, our experimental manipulation did not provide dispersal incentives to the test animals, which might have interfered with the decision of subordinates to cooperate. The experimental variation of the costs of resource acquisition for group members revealed significant effects on foraging, spacing, social interactions, and helping behaviour, which highlights the potential importance of ecological constraints on the behaviour, social structure and cooperation propensity in highly social vertebrates.
Population structure of the dusky pipefish (Syngnathus floridae) from the Atlantic and Gulf of Mexico, as revealed by mitochondrial DNA and microsatellite analyses
Authors: Mobley Kenyon B. , Small Clayton M. , Jue Nathaniel K. , Jones Adam G.
Published: April 2010

Aim  To elucidate the historical phylogeography of the dusky pipefish (Syngnathus floridae) in the North American Atlantic and Gulf of Mexico ocean basins.

Location  Southern Atlantic Ocean and northern Gulf of Mexico within the continental United States.

Methods  A 394‐bp fragment of the mitochondrial cytochrome b gene and a 235‐bp fragment of the mitochondrial control region were analysed from individuals from 10 locations. Phylogenetic reconstruction, haplotype network, mismatch distributions and analysis of molecular variance were used to infer population structure between ocean basins and time from population expansion within ocean basins. Six microsatellite loci were also analysed to estimate population structure and gene flow among five populations using genetic distance methods (FST, Nei’s genetic distance), isolation by distance (Mantel’s test), coalescent‐based estimates of genetic diversity and migration patterns, Bayesian cluster analysis and bottleneck simulations.

Results  Mitochondrial analyses revealed significant structuring between ocean basins in both cytochrome b (ΦST = 0.361, P < 0.0001; ΦCT = 0.312, P < 0.02) and control region (ΦST = 0.166, P < 0.0001; ΦCT = 0.128, P < 0.03) sequences. However, phylogenetic reconstructions failed to show reciprocal monophyly in populations between ocean basins. Microsatellite analyses revealed significant population substructuring between all locations sampled except for the two locations that were in closest proximity to each other (global FST value = 0.026). Bayesian analysis of microsatellite data also revealed significant population structuring between ocean basins. Coalescent‐based analyses of microsatellite data revealed low migration rates among all sites. Mismatch distribution analysis of mitochondrial loci supports a sudden population expansion in both ocean basins in the late Pleistocene, with the expansion of Atlantic populations occurring more recently.

Main conclusions  Present‐day populations of S. floridae do not bear the mitochondrial DNA signature of the strong phylogenetic discontinuity between the Atlantic and Gulf coasts of North America commonly observed in other species. Rather, our results suggest that Atlantic and Gulf of Mexico populations of S. floridae are closely related but nevertheless exhibit local and regional population structure. We conclude that the present‐day phylogeographic pattern is the result of a recent population expansion into the Atlantic in the late Pleistocene, and that life‐history traits and ecology may play a pivotal role in shaping the realized geographical distribution pattern of this species.
Oral bioavailability of P‐glycoprotein substrate drugs do not differ betweenABCB1‐1Δ andABCB1 wild type dogs
Authors: MEALEY K. L. , WAITING D. , RAUNIG D. L. , SCHMIDT K. R. , NELSON F. R.
Published: April 2010

Mealey, K.L., Waiting, D., Raunig, D.L., Schmidt, K.R., Nelson, F.R. Oral bioavailability of P‐glycoprotein substrate drugs do not differ betweenABCB1‐1Δ andABCB1 wild type dogs.J. vet. Pharmacol. Therap.33, 453–460.

Previous studies have indicated that intestinal P‐glycoprotein (P‐gp) limits the oral bioavailability of substrate drugs and alters systemic pharmacokinetics. In this study, dogs lacking functional P‐gp were used to determine the contribution of P‐gp to the oral bioavailability and systemic pharmacokinetics of several P‐gp substrate drugs. The P‐gp substrates quinidine, loperamide, nelfinavir, cyclosporin and the control (non P‐gp substrate) drug diazepam were individually administered intravenously and per os toABCB1‐1Δ dogs, which have a P‐gp null phenotype andABCB1 wildtype dogs.ABCB1‐1Δ dogs have been shown to have greater brain penetration of P‐gp substrates, but limited information is available regarding oral bioavailability of P‐gp substrate drugs in this animal model. Plasma drug concentration vs. time curves were generated and pharmacokinetic parameters were calculated for each drug. There were no differences in oral bioavailability betweenABCB1‐1Δ dogs andABCB1 wildtype dogs for any of the drugs studied, suggesting that intestinal P‐gp does not significantly affect intestinal absorption of these particular substrate drugs in ABCB1‐1Δ dogs. However, small sample sizes and individual variability in CYP enzyme activity may have affected the power of the study to detect the impact of P‐gp on oral bioavailability.
Fusicoccin affects cortical microtubule orientation in the isolated epidermis of sunflower hypocotyls
Authors: Burian A. , Hejnowicz Z.
Published: April 2010

Epidermal peels isolated from sunflower hypocotyls provide a convenient model to study the relationship between cortical microtubule orientation and strain rate. Extension of peels can be modulated using chemical treatment and mechanical stress, i.e., by adding a chemical to the incubation medium and applying a load exceeding the yield threshold for irreversible (plastic) strain. In this study, peels were pre‐incubated for ca. 12 h (long‐term pre‐incubation) or for 1 h (short‐term pre‐incubation). In the long‐term pre‐incubated peels, fusicoccin applied to the medium neither enhanced the rate of longitudinal plastic strain of loaded peels, nor affected microtubule orientation. However, fusicoccin increased the strain rate of short‐term, pre‐incubated peels and affected microtubule orientation in both extending (loaded) and non‐extending (unloaded) peels. Without fusicoccin, microtubule orientation was generally longitudinal or steep, whereas in fusicoccin‐treated unloaded peels it was transverse and oblique microtubules in peel portions corresponding to the apical part of the hypocotyl. Although the frequency of transverse orientation was increased through loading, there was no strong correlation between the rate of fusicoccin‐induced strain and microtubule orientation. It is hypothesized that the insensitivity of long‐term pre‐incubated peels to fusicoccin with respect to strain rate is due to a lack of active plasma membrane H+‐ATPases. Thus, the sensitivity of short‐term, pre‐incubated, unloaded (non‐extending) peels to fusicoccin, with respect to microtubule orientation, indicates that orientation might be affected by electric currents resulting from fusicoccin stimulation of H+‐ATPases.
Multispecies interactions among a plant parasite, a pollinator and a seed predator affect the reproductive output of an invasive plant, Cytisus scoparius
Authors: PRIDER JANE N. , FACELLI JOSÉ M. , WATLING JENNIFER R.
Published: April 2010

Interactions between species pairs are almost always mediated by interactions with other species. The outcomes of these multispecies interactions are often difficult to predict and are rarely studied. In addition to their theoretical importance, multispecies interactions are also important for management situations. Where multiple agents are used to control invasive species, interactions between agents may either enhance or reduce the impacts on the target species, or may simply have additive effects. In this study, conducted in a Mediterranean‐type woodland in Australia, we examined how the interaction between an invasive legume, Cytisus scoparius (Leguminosae), its pollinator, Apis mellifera and a seed predator, Bruchidius villosus (Bruchidae), are modified by a native hemiparasitic vine, Cassytha pubescens (Loranthaceae). The parasite had a direct negative effect on C. scoparius, reducing flowering by 50% and consequently fruit and seed production. Despite having fewer flowers, infected plants had the same proportion of ‘tripped’ flowers, an indirect measure of pollinator visitation, as uninfected plants; although fruit formed on infected plants it was more likely to abort prematurely. Seed predation by B. villosus was lower on parasite‐infected C. scoparius plants than in uninfected plants. Although Ca. pubescens had an antagonistic effect on B. villosus, in consort, the two agents reduced overall seed production by an average of 62%. The acquired parasite Ca. pubescens was more effective in reducing reproductive output than the introduced seed predator, B. villosus, and shows potential as a biocontrol agent for C. scoparius. We documented a subadditive effect of two biological enemies on the invasive species, where the acquired parasite had a stronger effect than the introduced seed predator.
High diversity of ammonia‐oxidizing archaea in permanent and seasonal oxygen‐deficient waters of the eastern South Pacific
Authors: Molina Verónica , Belmar Lucy , Ulloa Osvaldo
Published: April 2010

The community structure of putative aerobic ammonia‐oxidizing archaea (AOA) was explored in two oxygen‐deficient ecosystems of the eastern South Pacific: the oxygen minimum zone off Peru and northern Chile (11°S–20°S), where permanent suboxic and low‐ammonium conditions are found at intermediate depths, and the continental shelf off central Chile (36°S), where seasonal oxygen‐deficient and relatively high‐ammonium conditions develop in the water column, particularly during the upwelling season. The AOA community composition based on the ammonia monooxygenase subunit A (amoA) genes changed according to the oxygen concentration in the water column and the ecosystem studied, showing a higher diversity in the seasonal low‐oxygen waters. The majority of the archaeal amoA genotypes was affiliated to the uncultured clusters A (64%) and B (35%), with Cluster A AOA being mainly associated with higher oxygen and ammonium concentrations and Cluster B AOA with permanent oxygen‐ and ammonium‐poor waters. Q‐PCR assays revealed that AOA are an abundant community (up to 105amoA copies ml−1), while bacterial amoA genes from β proteobacteria were undetected. Our results thus suggest that a diverse uncultured AOA community, for which, therefore, we do not have any physiological information, to date, is an important component of the nitrifying community in oxygen‐deficient marine ecosystems, and particularly in rich coastal upwelling ones.