bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of Upf1p compensates for mitochondrial splicing deficiency independently of its role in mRNA surveillance
Authors: de Pinto B. , Lippolis R. , Castaldo R. , Altamura N.
Published: December 2004

In yeast the UPF1, UPF2 and UPF3 genes encode three interacting factors involved in translation termination and nonsense‐mediated mRNA decay (NMD). UPF1 plays a central role in both processes. In addition, UPF1 was originally isolated as a multicopy suppressor of mitochondrial splicing deficiency, and its deletion leads to an impairment in respiratory growth. Here, we provide evidence that inactivation of UPF2 or  UPF3,  like  that  of  UPF1,  leads  to  an  impairment in respiratory competence, suggesting that their products, Upf1p, Upf2p and Upf3p, are equivalently involved in mitochondrial biogenesis. In addition, however, we show that only Upf1p acts as a multicopy suppressor of mitochondrial splicing deficiency, and its activity does not require either Upf2p or Upf3p. Mutations in the conserved cysteine‐ and histidine‐rich regions and ATPase and helicase motifs of Upf1p separate the ability of Upf1p to complement the respiratory impairment of a Δupf1 strain from its ability to act as a multicopy suppressor of mitochondrial splicing deficiency, indicating that distinct pathways express these phenotypes. In addition, we show that, when overexpressed, Upf1p is not detected within mitochondria, suggesting that its role as multicopy suppressor of mitochondrial splicing deficiency is indirect. Furthermore, we provide evidence that cells overexpressing certain upf1 alleles accumulate a phosphorylated isoform of Upf1p. Altogether, these results indicate that overexpression of Upf1p compensates for mitochondrial splicing deficiency independently of its role in mRNA surveillance, which relies on Upf1p–Upf2p–Upf3p functional interplay.
Dynamics and processivity of 40S ribosome scanning on mRNA in yeast
Authors: Berthelot Karine , Muldoon Mark , Rajkowitsch Lukas , Hughes John , McCarthy John E. G.
Published: December 2004

The eukaryotic 40S ribosomal subunit locates the translation initiation codon on an mRNA via the so‐called scanning process that follows 40S binding to the capped 5′ end. This key step in translation is required for the expression of almost all eukaryotic genes, yet the mechanism and dynamics of scanning are unknown. We have performed quantitative studies in vivo and in vitro of the movement of yeast 40S ribosomes along 5′ untranslated regions (UTRs) of different lengths. 40S subunits perform cap‐dependent scanning with high processivity for more than 1700 nucleotides in cells of Saccharomyces cerevisiae. Moreover, the observed rates of expression indicate that scanning is performed by an untethered 40S subunit that has been released from the 5′ cap complex. Unexpectedly, the capability to maintain scanning competence on a long 5′ UTR is more dependent on the Ded1/Dbp1 type of helicase than on eIF4A or eIF4B. In a yeast cell‐free extract, scanning shows reduced processivity, with an estimated net 5′→3′ rate of approximately 10 nucleotides per second at 26°C. We have developed a biased bidirectional walking model of ribosomal scanning that provides a framework for understanding the above observations as well as other known quantitative and qualitative features of this process.
The Mycobacterium tuberculosis ino1 gene is essential for growth and virulence
Authors: Movahedzadeh Farahnaz , Smith Debbie A. , Norman Richard A. , Dinadayala Premkumar , Murray‐Rust Judith , Russell David G. , Kendall Sharon L. , Rison Stuart C. G. , McAlister Mark S. B. , Bancroft Gregory J. , McDonald Neil Q. , Daffe Mamadou , Av‐Gay Yossef , Stoker Neil G.
Published: December 2004

Inositol is utilized by Mycobacterium tuberculosis in the production of its major thiol and of essential cell wall lipoglycans. We have constructed a mutant lacking the gene encoding inositol‐1‐phosphate synthase (ino1), which catalyses the first committed step in inositol synthesis. This mutant is only viable in the presence of extremely high levels of inositol. Mutant bacteria cultured in inositol‐free medium for four weeks showed a reduction in levels of mycothiol, but phosphatidylinositol mannoside, lipomannan and lipoarabinomannan levels were not altered. The ino1 mutant was attenuated in resting macrophages and in SCID mice. We used site‐directed mutagenesis to alter four putative active site residues; all four alterations resulted in a loss of activity, and we demonstrated that a D310N mutation caused loss of the active site Zn2+ ion and a conformational change in the NAD+ cofactor.
The RhaS activator controls the Erwinia chrysanthemi 3937 genes rhiN, rhiT and rhiE involved in rhamnogalacturonan catabolism
Authors: Hugouvieux‐Cotte‐Pattat Nicole
Published: December 2004

Erwinia chrysanthemi causes soft‐rot diseases of various plants by enzymatic degradation of the pectin in plant cell walls. The linear regions of pectin are composed of an acidic sugar, d‐galacturonic acid. The ramified regions of pectin also include neutral sugars, and are rich in l‐rhamnose residues. E. chrysanthemi is able to degrade these polysaccharides, polygalacturonate and rhamnogalacturonate. In E. chrysanthemi, the production of pectinases acting on linear regions is induced in the presence of polygalacturonate by a mechanism involving the repressor KdgR. The induction of the two adjacent E. chrysanthemi genes, designated rhiT and rhiN, is maximal after the simultaneous addition of both polygalacturonate and l‐rhamnose. The rhiT product is homologous to the oligogalacturonide transporter TogT of E. chrysanthemi. The rhiN product is homologous to various proteins of unknown function, including a protein encoded by the plant‐inducible locus picA of Agrobacterium tumefaciens. Both rhiT and rhiN are highly induced during plant infection. Various data suggest that RhiT and RhiN are involved in rhamnogalacturonate catabolism. RhiN is able to degrade the oligomers liberated by the rhamnogalacturonate lyase RhiE. The induction of the rhiTN operon in the presence of polygalacturonate results from control by the repressor KdgR. The additional induction of these genes by rhamnose is directly mediated by RhaS, a protein homologous to the activator of rhamnose catabolism in Escherichia coli. The virulence of an E. chrysanthemi rhaS mutant towards different host plants was clearly reduced. In this phytopathogenic bacterial species, RhaS positively regulates the transcription of the rhaBAD operon, involved in rhamnose catabolism, of the rhiE gene and of the rhiTN operon. The regulator RhaS plays a larger role in E. chrysanthemi than in other enterobacteria. Indeed, the RhaS control is not restricted to the catabolism of rhamnose but is extended to the degradation of plant polysaccharides that contain this sugar.
The d,d‐carboxypeptidase PBP3 organizes the division process of Streptococcus pneumoniae
Authors: Morlot Cécile , Noirclerc‐Savoye Marjolaine , Zapun André , Dideberg Otto , Vernet Thierry
Published: December 2004

Bacterial division requires the co‐ordination of membrane invagination, driven by the constriction of the FtsZ‐ring, and concomitant cell wall synthesis, performed by the high‐molecular‐weight penicillin‐binding proteins (HMW PBPs). Using immunofluorescence techniques, we show in Streptococcus pneumoniae that this co‐ordination requires PBP3, a d,d‐carboxypeptidase that degrades the substrate of the HMW PBPs. In a mutant deprived of PBP3, the apparent rings of HMW PBPs and that of FtsZ are no longer co‐localized. In wild‐type cells, PBP3 is absent at the future division site and present over the rest of the cell surface, implying that the localization of the HMW PBPs at mid‐cell depends on the availability of their substrate. FtsW, a putative translocase of the substrate of the PBPs, forms an apparent ring that is co‐localized with the septal HMW PBPs throughout the cell cycle of wild‐type cells. In particular, the constriction of the FtsW‐ring occurs after that of the FtsZ‐ring, with the same delay as the constriction of the septal PBP‐rings. However, in the absence of PBP3, FtsW remains co‐localized with FtsZ in contrast to the HMW PBPs. Our work reveals an unexpected complexity in the relationships between the division proteins. The consequences of the absence of PBP3 indicate that the peptidoglycan composition is central to the co‐ordination of the division process.
The histological appearances of Nissen‐type fundoplication in the ferret
Authors: Richards C. A. , Smith V. V. , Milla P. J. , Spitz L. , Andrews P. L. R.
Published: December 2004

Abstract  Nissen fundoplication is of proven effectiveness in the surgical control of gastro‐oesophageal reflux. However, our understanding of the effects of fundoplication upon foregut physiology is incomplete and post‐operative symptoms are often poorly understood. This experimental study aimed systematically to characterize the tissue response to fundoplication in an animal model, to improve understanding of the effects of anti‐reflux surgery upon foregut physiology. Nissen‐type fundoplication was performed in the ferret, and the tissue response at 3 months examined histologically. Sham‐operated animals that underwent laparotomy but no dissection or wrap, acted as controls. In fundoplicated animals, serosal fibrosis was observed in the gut wall, with patchy replacement of muscle by fibrous tissue. The ventral and dorsal vagal nerve trunks were identified intact within the wrap. In cases where the wrap had spontaneously disrupted, fibrosis was more extensive and there was evidence of nerve damage. This is the first systematic description of the histopathological response to Nissen fundoplication. In the intact wrap, the vagal trunks appear spared, but there is fibrosis in the serosa, extending into the muscularis of the distal oesophagus and region of the cardia. These findings are discussed in relation to the effects of Nissen fundoplication upon gastric physiology and postoperative symptoms.
Nicotinic transmission at functionally distinct synapses in descending reflex pathways of the rat colon
Authors: Bian X‐C. , Bornstein J. C. , Bertrand P. P.
Published: December 2004

Abstract  We examined descending reflex pathways in the rat colon using intracellular recording techniques. Inhibitory junction potentials (IJPs) were recorded from circular smooth muscle when descending pathways were excited by combined mucosal compression and distension. IJPs were reduced to 71% of control when synaptic transmission was blocked in the oral stimulation chamber of a divided organ bath suggesting that two reflex pathways exist, the one involving descending sensory neurones and the other involving descending interneurones. Hexamethonium (200 μmol L−1) in the recording chamber abolished reflexly evoked IJPs, while in the stimulation chamber, it was as effective as synaptic blockade. When hexamethonium was added to a chamber lying between the stimulation and recording chambers, it again sharply depressed IJPs to 27% of control; an extent similar to synaptic blockade. A P2 receptor antagonist did not reveal any purinergic neurotransmission. Either granisetron (5‐HT3 receptor antagonist, 1 μmol L−1) or SB204070 (5‐HT4 receptor antagonist, 1 μmol L−1) in the stimulation chamber significantly decreased IJPs; these decreases were not additive. We conclude that some sensory neurones and interneurones in rat colon have long anally projecting axons and that acetylcholine, acting via nicotinic receptors, is the primary neurotransmitter from sensory neurones, to inhibitory motor neurones and between interneurones.
Localization of protein kinase C theta immunoreactivity to interstitial cells of Cajal in guinea‐pig gastrointestinal tract
Authors: Southwell B. R.
Published: December 2004

Abstract In the gastrointestinal tract, interstitial cells of Cajal (ICC) are located between nerve fibres and muscle cells and have a role in neuromuscular transmission and muscle contractility. Protein kinase C (PKC) is involved in modulation of muscle contractility by neurotransmitters, but it is not known if PKC has a role in ICC. There are 11 different PKC isoforms. The presence of PKC isoforms in ICC in guinea‐pig gastrointestinal tract was examined using fluorescence immunohistochemistry and confocal microscopy. Segments of guinea‐pig stomach, duodenum, ileum, proximal and distal colon were fixed in zambonis fixative. Frozen sections and wholemounts were incubated with anti‐PKC antibodies (α,β,δ,ε,γ,ι,λ, μ,θ) followed by fluorescent secondary antibody. Only PKC theta (θ) immunoreactivity was found in ICC. None of the other PKC isoforms (α,β,δ,ε,γ,ι,λ, μ) localized to the ICC. PKCθimmunoreactivity was prominent in ICC located between the circular and longitudinal muscle layers (ICC‐MY) in all regions except stomach and within the circular muscle (ICC‐IM) in the large intestine. PKCθwas not present in ICC in the deep muscular plexus in either duodenum or ileum. PKCθimmunoreactivity was present in the cell body and proximal processes of the ICC. The cells containing PKCθalso contained cKit confirming the cells were ICC. ICC‐MY in the ileum also contained the neurokinin (NK) 1 receptor. In conclusion, PKCθis present in pacemaker ICC, but its function is not yet known. Functional studies will be needed to determine the role of this kinase in ICC. Knowing the second messenger cascades and being able to manipulate subpopulations of ICC will add to our understanding of the molecular and cell biology of ICC networks within the gastrointestinal tract and may ultimately help in understanding the aetiology of some gastrointestinal motor pathologies.
Differential effects of motilin on interdigestive motility of the human gastric antrum, pylorus, small intestine and gallbladder
Authors: Luiking Y. C. , Akkermans L. M. A. , Van Der Reijden A. C. , Peeters T. L. , Van Berge‐Henegouwen G. P.
Published: December 2004

Abstract  Motilin was infused in this study with the aim of examining refractory characteristics for motilin stimulation of antral phase III and fasting gallbladder emptying. Moreover, interdigestive pyloric and small intestinal motility from duodenum to ileum were studied, as these may be target organs for motilin. Eight fasting, healthy male volunteers received, on separate subsequent days, repeated infusions of13leucine–motilin (8 pmol (kg min)−1 for 5 min) or saline at 30 min after phase IIIs in the duodenum. Interdigestive motility of the antrum, pylorus, duodenum, jejunum and ileum was measured for maximum 10 h by using a 21‐lumen perfused catheter. Gallbladder motility was measured by ultrasonography. Motilin infusions induced antral phase IIIs, but only after a preceding phase III of duodenal origin. Under this condition, time‐interval to phase III at the duodenal recording site was 30 ± 13 (SEM) min after motilin, compared with 79 ± 14 min after saline (P < 0.01), and compared with 121 ± 13 min for motilin infusion following an antral phase III (P < 0.001). Motilin did not affect small intestinal motility or isolated pyloric pressure waves (IPPWs). However, the number of IPPWs was significantly affected by the origin of the preceding phase III, irrespective of whether motilin or saline was infused. Gallbladder volume decreased significantly within 10 min after each motilin infusion. We conclude that this study clearly demonstrates differential regional effects of motilin. Motilin initiates antral phase IIIs, but stimulation is subject to a refractory period which is clearly prolonged after a preceding antral phase III. Motilin induced gallbladder emptying, however, is not subject to a refractory state. Small intestinal phase IIIs as well as pyloric IPPWs are not affected by motilin.
Electrogastrography: a document prepared by the gastric section of the American Motility Society Clinical GI Motility Testing Task Force
Authors: Parkman H. P. , Hasler W. L. , Barnett J. L. , Eaker E. Y.
Published: December 2004

Abstract The objective of this document is to present the consensus opinion of the American Motility Society Clinical GI Motility Testing Task Force on the performance and clinical utility of electrogastrography (EGG). EGG is a non‐invasive means of recording human gastric myoelectrical activity or slow waves from cutaneous leads placed over the stomach. In healthy volunteers, EGG tracings exhibit sinusoidal waveforms with a predominant frequency of 3 cycles per minute (cpm). Clinical studies have shown good correlation of these cutaneous recordings with those acquired from serosally implanted electrodes. The amplitude of the EGG waveform increases with ingestion of caloric or non‐caloric meals. Some patients with nausea, vomiting, or other dyspeptic symptoms exhibit EGG rhythm disturbances or blunting of meal‐evoked EGG signal amplitude increases. These abnormalities correlate to some degree with delayed gastric emptying of solids. In selected patients, EGG may be complementary to gastric emptying testing. To date, no therapies have convincingly demonstrated in controlled studies that correcting abnormalities detected by EGG improves upper gastrointestinal symptoms. Proposed clinical indications for performance of EGG in patients with unexplained nausea, vomiting and dyspeptic symptoms must be validated by prospective controlled investigations.
Effects of Schistosoma mansoni infection on somatostatin and somatostatin receptor 2A expression in mouse ileum
Authors: De Jonge F. , Van Nassauw L. , De Man J. G. , De Winter B. Y. , Van Meir F , Depoortere I. , Peeters T. L. , Pelckmans P. A. , Van Marck E. , Timmermans J‐P.
Published: December 2004

Abstract  Intestinal schistosomiasis is accompanied by motility‐related dysfunctions but the underlying mechanisms are not well‐known. Therefore, the presence and effects on intestinal contractility of somatostatin (SOM) and its receptor, SSTR2A, were investigated in the ileum of normal and infected mice. The distribution of SOM and SSTR2A was visualized using immunocytochemistry. Radioimmunoassay combined with oogram studies was performed to determine SOM levels and contractility measurements were determined in organ bath experiments. Schistosomiasis resulted in a significant decrease in somatostatin‐positive endocrine cells, whereas the number of somatostatin‐immunoreactive (IR) neuronal cell bodies did not change. From 8 weeks postinfection onwards, an increase was noted in somatostatin‐IR nerve fibres in both villi and granulomas. The staining intensity for SSTR2A, expressed in somatostatin‐negative myenteric cholinergic neurones, increased during infection suggesting an upregulation of this receptor. SOM levels were negatively correlated with the number of eggs during the acute phase, and were elevated during the chronic phase. Pharmacological experiments revealed that schistosomiasis diminished the inhibitory effect of SOM on neurogenic contractions. We can conclude that schistosomiasis influences the distribution and expression levels of SOM and SSTR2A in the murine ileum, which might explain the changed motility pattern.
Neural regulation of tone in the oesophageal body: in vivo barostat assessment of volume–pressure relationships in the feline oesophagus
Authors: Zhang X. , Tack J. , Janssens J. , Sifrim D. A.
Published: December 2004

Abstract  Recent combined manometric–barostat studies demonstrated that the oesophageal body exhibits both peristaltic contractions and tone. This study further characterized the neural modulation of tone in the feline oesophageal body. Simultaneous oesophageal barostat and manometry were performed in 20 adult cats under ketamine sedation. Oesophageal tone and peristalsis were assessed in the distal smooth muscle oesophagus. Cholinergic modulation was studied using neostigmine, erythromycin, atropine and vagotomy. Nitrergic regulation was assessed using sildenafil to increase cellular cyclic guanosine monophosphate and the nitric oxide synthase blocker Nω‐nitro‐l‐arginine (l‐NNA). The presence of a tonic contractile activity in the distal oesophageal body was confirmed. Peristaltic contractions proceeded along the oesophageal body over the background tonic contraction. Neostigmine and erythromycin enhanced (20–30%) whereas bilateral vagotomy and atropine strongly decreased oesophageal tone (50–60%). However, l‐NNA increased (40%) and sildenafil decreased oesophageal tone (30%). Therefore, tonic contractile activity in the oesophageal body is mainly caused by a continuous cholinergic excitatory input. A nitric oxide inhibitory mechanism may have a complementary role in the regulation of oesophageal tone.
Nitrergic–purinergic interactions in rat distal colon motility
Authors: Crombruggen K. Van , Lefebvre R. A.
Published: December 2004

Abstract  Responses of rat distal colon circular muscle strips to exogenous nitric oxide (NO) and adenosine 5′‐triphosphate (ATP) and to electrical field stimulation (EFS) were assessed in the absence/presence of various agents that interfere with nitrergic–purinergic pathways.

Exogenous NO (10−6 to 10−4 mol L−1) elicited concentration‐dependent, tetrodotoxin (TTX)‐insensitive relaxations. The soluble guanylyl‐cyclase (sGC) inhibitor 1H[1,2,4,]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) reduced duration and amplitude; the small conductance Ca2+‐sensitive K+ (SK)‐channel blocker apamin (APA) only shortened the relaxations. ODQ + APA showed a marked inhibitory effect on duration and amplitude.

TTX, APA, the NO‐synthase inhibitor N(omega)‐nitro‐l‐arginine methyl ester (l‐NAME) and the purinergic receptor P2Y antagonist Reactive Blue 2 (RB2) shortened the relaxations by exogenous ATP (10−3 mol L−1) but did not influence the amplitude. ODQ had no effect. TTX + l‐NAME did not yield a more pronounced inhibitory effect than TTX alone. The effect of ATP‐γ‐S was similar to that of ATP.

Electrical field stimulation (EFS) (40 V, 0.05 ms, 0.5–4 Hz for 30 s) yielded TTX‐sensitive relaxations that were not altered by l‐NAME, ODQ or RB2. APA shortened the relaxations. l‐NAME + APA nearly abolished these relaxations. ODQ + APA and RB2 +l‐NAME reduced the duration.

These results suggest that distinct sets of small conductance SK‐channels are involved in the amplitude and the duration of the relaxations and that NO increases their sensitivity to NO and ATP via guanosine 3′,5′‐cyclic monophosphate (cGMP). ATP elicits relaxations via P2Y receptors with subsequent activation of SK‐channels and induces neuronal release of NO. Both nitrergic and purinergic pathways must be blocked to inhibit EFS‐induced relaxations.
The expression and role of Fas ligand in intestinal inflammation
Authors: Sayani F. A. , Keenan C. M. , Van Sickle M. D. , Amundson K. R. , Parr E. J. , Mathison R. D. , MacNaughton W. K. , Braun J. E. A. , Sharkey K. A.
Published: December 2004

Abstract  Fas ligand (FasL) is involved in the pathogenesis of inflammatory diseases and immune privilege. We examined the expression of FasL in the enteric nervous system (ENS) in murine colitis and guinea‐pig ileitis. We studied FasL immunoreactivity, functional integrity of the ENS, severity of colitis, and distribution of neutrophils in wild type and B6/gld mice that lack functional FasL. In ileitis, the distribution of FasL, CD4+ and CD8+ T cells was examined. FasL expression was increased in the ENS of wild type mice with colitis, but decreased labelling of nerve fibres was noted in B6/gld mice. Neutrophils were more abundant and widely distributed in B6/gld mice. Colitis was more severe and persistent in B6/gld mice 7 days after induction. Functional parameters of intestinal secretion and motility in B6/gld mice were the same as controls. In ileitis, FasL expression was increased in the guinea‐pig ENS and returned to control levels following the resolution of inflammation. While T cells were not present in the ENS of controls, they were observed during inflammation, but were excluded from ganglia. The number of enteric neurons was unchanged over the course of inflammation. The expression of FasL is altered in intestinal inflammation and contributes to its resolution in experimental colitis.
Effects of the probiotic yeast Saccharomyces boulardii on the neurochemistry of myenteric neurones in pig jejunum
Authors: Kamm K. , Hoppe S. , Breves G. , Schröder B. , Schemann M.
Published: December 2004

Abstract  We studied the effects of food supplementation with Saccharomyces boulardii (S. boulardii; synonym S. cerevisiae HANSEN CBS 5926; 1 g per day for 9 days) on the presence and co‐localization patterns of neuronal markers in myenteric neurones of the pig jejunum. The pan neuronal marker Hu revealed no change in the number of neuronal cell bodies per ganglion (37 ± 7 in control vs 34 ± 9 in the S. boulardii group). Ranked by size the following cell populations were identified: choline acetyltransferase (ChAT), calbindin‐28k (CALB), substance P (SP), neurofilament 160 kD (NF‐160), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), calcitonin gene‐related peptide (CGRP), calretinin (CALRET). We found a significant decrease in the number of CALB myenteric neurones in animals which received S. boulardii supplemented diet. None of the other neuronal markers revealed any difference between controls and S. boulardii treated animals. The study reports transmitter‐localization patterns in the myenteric plexus of the pig jejunum and provides evidence that changes in the neurochemistry of enteric neurones occur with S. boulardii supplemented diet. Although only CALB expression was altered and the functional significance of this finding remains unknown, our study identified a possible new effector level of probiotics in the gut.
Isolation and characterization of resident macrophages from the smooth muscle layers of murine small intestine
Authors: Ozaki H. , Kawai T. , Shuttleworth C.W. , Won K.‐J. , Suzuki T. , Sato K. , Horiguchi H. , Hori M. , Karaki H. , Torihashi S. , Ward S. M. , Sanders K. M.
Published: December 2004

Abstract  Macrophages within the murine tunica muscularis were isolated and cultured for physiological studies. Following dispersion, macrophages were identified by phagocytotic activity of fluorescein isothiocyanate (FITC)‐dextran. Immediately following isolation, macrophages were rounded and possessed fluorescent granula but developed a ramified shape after 3–4 days in culture. Resident and cultured macrophages were immunopositive for F4/80 and I‐Ad/I‐Ed. Greater than 90% of F4/80 positive cultured cells were FITC‐dextran positive. Macrophages had resting membrane potentials (RMP) of −33.3 ± 1.5 mV after 1 day in culture, which increased to −53.9 ± 4.4 mV after 3–4 days. The change in RMP was associated with the development of an inward rectifying K+ current, and a decrease in a voltage‐dependent, inactivating outward current. After 3–4 days in culture the inflammatory mediated substances adenosine triphosphate (ATP), platelet‐activating factor and bacterial lipopolysaccharide induced increases in cytoplasmic Ca2+ ([Ca2+]i). Forskolin suppressed the ATP‐induced increase in [Ca2+]i. Macrophages exhibited oxidative bursts, measured by oxidation of dihydrorhodamine‐123 to rhodamine‐123. Oxidative bursts coincided with a reduction in intracellular pH. Macrophages expressed a proton conductance that may participate in pH maintenance during reactive oxygen production. These results suggest that resident macrophages in the intestine may play a role in the immunological protection of the gut.
Neurological aspects of osteopetrosis
Authors: Steward C. G.
Published: December 2004

The osteopetroses are caused by reduced activity of osteoclasts which results in defective remodelling of bone and increased bone density. They range from a devastating neurometabolic disease, through severe malignant infantile osteopetrosis (OP) to two more benign conditions principally affecting adults [autosomal dominant OP (ADO I and II)]. In many patients the disease is caused by defects in either the proton pump [the a3 subunit of vacuolar‐type H(+)‐ATPase, encoded by the gene variously termed ATP6i or TCIRG1] or the ClC‐7 chloride channel (ClCN7 gene). These pumps are responsible for acidifying the bone surface beneath the osteoclast. Although generally thought of as bone diseases, the most serious consequences of the osteopetroses are seen in the nervous system. Cranial nerves, blood vessels and the spinal cord are compressed by either gradual occlusion or lack of growth of skull foramina. Most patients with OP have some degree of optic atrophy and many children with severe forms of autosomal recessive OP are rendered blind; optic decompression is frequently attempted to prevent the latter. Auditory, facial and trigeminal nerves may also be affected, and hydrocephalus can develop. Stenosis of both arterial supply (internal carotid and vertebral arteries) and venous drainage may occur. The least understood form of the disease is neuronopathic OP [OP and infantile neuroaxonal dystrophy, MIM (Mendelian inheritance in man) 600329] which causes rapid neurodegeneration and death within the first year. Although characterized by the finding of widespread axonal spheroids and accumulation of ceroid lipofuscin, the biochemical basis of this disease remains unknown. The neurological complications of this disease and other variants are presented in the context of the latest classification of the disease.
Three monkeys nearing extinction in the forest reserves of eastern Côte d'lvoire
Authors: McGraw W. Scott
Published: December 2004

Surveys were carried out in forest reserves in eastern Côte d'lvoire in 1997 to investigate the status of three primate taxa believed to be on the verge of extinction. The findings indicate that Procolobus badius waldroni may be extinct, and that Cercopithecus diana roloway and Cercocebus atys lunulatus may become so unless urgent action is taken.
The prenatal development of the human cerebellar field in Down syndrome
Authors: Lomholt J.F. , Keeling J.W. , Hansen B.F. , Ono T. , Stoltze K. , Kjær I.
Published: December 2004

Structured Abstract

Authors – Lomholt JF, Keeling JW, Hansen BF, Ono T,Stoltze K, Kjær I

Objectives – To describe the development of the osseous field enclosing the cerebellum and part of the brain stem (the neuro‐osteological cerebellar field) in Down syndrome, and compare the development with normal developmental standard of the field.

Design – Radiographic, cephalometric and histologic examination of 58 legally or spontaneously aborted Down syndrome prenatal human fetuses; crown–rump length of 80–255 mm and approximate gestational age from 13 to 26 weeks.

Results – The growth of the Down syndrome cerebellar field is smaller in the sagittal and vertical directions than in normal fetuses.

Conclusion – In the present study the pathological development of the cerebellar field was described in a genotypic sample. In combining normal and pathological development of neural and osseous tissues a better understanding of the genotype/phenotype interactions is attainable and fields of common gene expression maybe defined.
MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years?
Authors: Bernatchez L. , Landry C.
Published: December 2004

Elucidating how natural selection promotes local adaptation in interaction with migration, genetic drift and mutation is a central aim of evolutionary biology. While several conceptual and practical limitations are still restraining our ability to study these processes at the DNA level, genes of the major histocompatibility complex (MHC) offer several assets that make them unique candidates for this purpose. Yet, it is unclear what general conclusions can be drawn after 15 years of empirical research that documented MHC diversity in the wild. The general objective of this review is to complement earlier literature syntheses on this topic by focusing on MHC studies other than humans and mice. This review first revealed a strong taxonomic bias, whereby many more studies of MHC diversity in natural populations have dealt with mammals than all other vertebrate classes combined. Secondly, it confirmed that positive selection has a determinant role in shaping patterns of nucleotide diversity in MHC genes in all vertebrates studied. Yet, future tests of positive selection would greatly benefit from making better use of the increasing number of models potentially offering more statistical rigour and higher resolution in detecting the effect and form of selection. Thirdly, studies that compared patterns of MHC diversity within and among natural populations with neutral expectations have reported higher population differentiation at MHC than expected either under neutrality or simple models of balancing selection. Fourthly, several studies showed that MHC-dependent mate preference and kin recognition may provide selective factors maintaining polymorphism in wild outbred populations. However, they also showed that such reproductive mechanisms are complex and context-based. Fifthly, several studies provided evidence that MHC may significantly influence fitness, either by affecting reproductive success or progeny survival to pathogens infections. Overall, the evidence is compelling that the MHC currently represents the best system available in vertebrates to investigate how natural selection can promote local adaptation at the gene level despite the counteracting actions of migration and genetic drift. We conclude this review by proposing several directions where future research is needed.
Two species of feminizing microsporidian parasite coexist in populations of Gammarus duebeni
Authors: Ironside J. E. , Smith J. E. , Hatcher M. J. , Sharpe R. G. , Rollinson D. , Dunn A. M.
Published: December 2004

The amphipod crustacean Gammarus duebeni hosts two species of vertically transmitted microsporidian parasites, Nosema granulosis and Microsporidium sp. A. Here it is demonstrated that these co-occurring parasite species both cause infected females to produce female-biased broods. A survey of European G. duebeni populations demonstrates that these two parasites co-occur in six of 10 populations. These findings contrast with the theoretical prediction that two vertically transmitted feminizing parasites should not coexist in a panmictic population of susceptible hosts at equilibrium. Possible explanations for the co-occurrence of the two feminizing microsporidia in G. duebeni include the recent invasion of a new parasite, horizontal transmission of one or both parasites and the spread of alleles for resistance to the dominant parasite in host populations.
A linear dominance hierarchy among clones in chimeras of the social amoeba Dictyostelium discoideum
Authors: Fortunato A. , Queller D. C. , Strassmann J. E.
Published: December 2004

Amoebae from different clones of Dictyostelium discoideum aggregate into a common slug, which migrates towards light for dispersal, then forms a fruiting body consisting of a somatic, dead stalk, holding up a head of living spores. Contributions of two clones in a chimera to spore and stalk are often unequal, with one clone taking advantage of the other's stalk contribution. To determine whether there was a hierarchy of exploitation among clones, we competed all possible pairs among seven clones and measured their relative representation in the prespore and prestalk stages and in the final spore stage. We found a clear linear hierarchy at the final spore stage, but not at earlier stages. These results suggest that there is either a single principal mechanism or additive effects for differential contribution to the spore, and that it involves more than spore/stalk competition.
Correlations between ultraviolet coloration, overwinter survival and offspring sex ratio in the blue tit
Authors: Griffith S. C. , Örnborg J. , Russell A. F. , Andersson S. , Sheldon B. C.
Published: December 2004

We studied the correlations between offspring sex ratio, UV coloration and overwinter survival in a population of blue tits, breeding in Gotland, Sweden, over three consecutive breeding seasons. In 2 of 3 years, we found that females paired to males with relatively brighter UV-coloration produced a greater proportion of sons in their broods, and that this effect was significant with all 3 years combined, despite a significant year by male UV interaction. In addition, we found other correlates of sex ratio (breeding time, female age and clutch size) in some, but not all years, and some of these showed significantly different relationships with sex ratio between years. In both years for which data were available, there were indications that males with relatively brighter UV coloration, and that paired with females that produced male-biased clutches, were more likely to survive to the next year. In addition, we also found that in both males and females, individuals produced similar sex ratios in consecutive years. Because correlations with the sex ratio may be expected to be weak, variation in results between years within the same population may be explained by low statistical power or genuine biological differences. Our results suggest that conclusions about sex ratio variation in birds should be based on multiple years. The correlations that we found in some years of this study are consistent with models of adaptive sex ratio adjustment in response to mate quality. However, careful experimental work is required to provide tests of the assumptions of these models, and should be a priority for future work.
Latitudinal countergradient variation in the common frog (Rana temporaria) development rates – evidence for local adaptation
Authors: Laugen A. T. , Laurila A. , Räsänen K. , Merilä J.
Published: December 2004

Adaptive genetic differentiation along a climatic gradient as a response to natural selection is not necessarily expressed at phenotypic level if environmental effects on population mean phenotypes oppose the genotypic effects. This form of cryptic evolution – called countergradient variation – has seldom been explicitly demonstrated for terrestrial vertebrates. We investigated the patterns of phenotypic and genotypic differentiation in developmental rates of common frogs (Rana temporaria) along a ca. 1600 km latitudinal gradient across Scandinavia. Developmental rates in the field were not latitudinally ordered, but displayed large variation even among different ponds within a given latitudinal area. In contrast, development rates assessed in the laboratory increased strongly and linearly with increasing latitude, suggesting a genetic capacity for faster development in the northern than the southern larvae. Experiments further revealed that environmental effects (temperature and food) could easily override the genetic effects on developmental rates, providing a possible mechanistic explanation as to why the genetic differentiation was not seen in the samples collected from the wild. Our results suggest that the higher developmental rates of the northern larvae are likely to be related to selection stemming from seasonal time constrains, rather than from selection dictated by low ambient temperatures per se. All in all, the results provide a demonstration of environmental effects concealing substantial latitudinally ordered genetic differentiation understandable in terms of adaptation to clinal variation in time constrains.
Adaptive sex-specific life history plasticity to temperature and photoperiod in a damselfly
Authors: De Block M. , Stoks R.
Published: December 2004

We investigated four predictions about how temperature, photoperiod and sex affect the life history plasticity and foraging activity of a damselfly. (i) As predicted, increased temperatures increased foraging activity and growth rates, but in contrast with the prediction, late photoperiod (high time stress) did not affect foraging activity and growth rate. (ii) Unexpectedly, the increase in growth rate at increasing temperatures was not larger under high time stress. (iii) As predicted, age and size at emergence decreased at higher temperatures and at the late photoperiod. Temperature-induced life history shifts were direct or the result of behavioural growth mediation depending on the temperature range. Photoperiod-induced life history shifts were direct. (iv) As predicted, males emerged before females but at a smaller size. The degree of sexual size dimorphism was influenced by the joint effects of temperature and photoperiod. We could only detect genetic variation in size plasticity to photoperiod. The match between the sex-specific life history responses to temperature and photoperiod and predictions by relevant optimality models suggests adaptive life history plasticity to these variables.
The effects of parasitism and inbreeding on the competitive ability in Daphnia magna: evidence for synergistic epistasis
Authors: Salathé P. , Ebert D.
Published: December 2004

Synergistic epistasis for fitness is often assumed in models of how selection acts on the frequency and distribution of deleterious mutations. Evidence for synergistic epistasis would exist if the logarithm of fitness declines more quickly with number of deleterious mutations, than predicted by a linear decline. This can be studied indirectly by quantifying the effect of different levels of inbreeding on fitness. Here, six sets (different genetic backgrounds) of three increasingly inbred Daphnia magna clones were used to assess their relative fitness according to changes in frequency in a competition experiment against a tester clone. A novelty of the mating procedure was that the inbreeding coefficients (F) of the three clones belonging to each set increased in steps of 0.25 independent of the (unknown) inbreeding coefficient of the common ancestor. The equal increase of the inbreeding coefficients is important, because deviations influence the quantification of inbreeding depression, its variance and the detection of epistasis. In a simple mathematical model we show that when working with a partially inbred population inbreeding depression is underestimated, the variance of fitness is increased, and the detection of epistasis more difficult. Further, to examine whether an interaction between inbreeding and parasitism exists, each inbred clone was tested with and without a microsporidium infection (Octosporea bayeri). We found a nonlinear decrease of the logarithm of fitness across the three levels of inbreeding, indicating synergistic epistasis. The interaction term between parasitism and inbreeding was not significant. Our results suggest that deleterious mutations may be purged effectively once the level of inbreeding is high, but that parasitism seems not to influence this effect.
Sexual conflict and indirect benefits
Authors: Cameron E. , Day T. , Rowe L.
Published: December 2004

Recent work on sexual selection and sexual conflict has explored the influence of indirect effects on the evolution of female mating behaviour. It has been suggested that the importance of these effects has been underestimated and that the influence of indirect effects may actually be of relatively greater significance than direct effects. Additionally, it has also been suggested that all indirect effects, both good genes and sexy son, are qualitatively equivalent. Here a counterpoint to these suggestions is offered. We argue two main points: (1) it is unlikely that indirect effects will commonly outweigh direct effects, and (2) that there are important differences between good genes and sexy son indirect effects that must be recognized. We suggest that acknowledgement of these distinctions will lead to increased understanding of processes operating in both sexual conflict and sexual selection.
Sex-specific associative learning cues and inclusive fitness benefits in the Seychelles warbler
Authors: Richardson D. S. , Burke T. , Komdeur J.
Published: December 2004

In cooperative breeding vertebrates, indirect fitness benefits would be maximized by subordinates that accurately assess their relatedness to group offspring and preferentially help more closely related kin. In the Seychelles warbler (Acrocephalus sechellensis), we found a positive relationship between subordinate-nestling kinship (determined using microsatellite marker genotypes) and provisioning rates, but only for female subordinates. Female subordinates that helped were significantly more related to the nestlings than were nonhelpers, and the decision to help appears to be based on associative learning cues. High levels of female infidelity means that subordinates cannot trust their legitimacy through the male line, consequently they appear to use the continued presence of the primary female, but not the primary male, as a reliable cue to determine when to feed nestlings. By using effective discrimination, female subordinates are able to maximize the indirect benefits gained within a cooperative breeding system otherwise driven primarily by direct breeding benefits.
Directional changes in sexual size dimorphism in shorebirds, gulls and alcids
Authors: Lindenfors P. , Székely T. , Reynolds J. D.
Published: December 2004

The Charadrii (shorebirds, gulls and alcids) are one of the most diverse avian groups from the point of view of sexual size dimorphism, exhibiting extremes in both male-biased and female-biased dimorphism, as well as monomorphism. In this study we use phylogenetic comparative analyses to investigate how size dimorphism has changed over evolutionary time, distinguishing between changes that have occurred in females and in males. Independent contrasts analyses show that both body mass and wing length have been more variable in males than in females. Directional analyses show that male-biased dimorphism has increased after inferred transitions towards more polygynous mating systems. There have been analogous increases in female-biased dimorphism after transitions towards more socially polyandrous mating systems. Changes in dimorphism in both directions are attributable to male body size changing more than female body size. We suggest that this might be because females are under stronger natural selection constraints related to fecundity. Taken together, our results suggest that the observed variation in dimorphism of Charadrii can be best explained by male body size responding more sensitively to variable sexual selection than female body size.
Evidence for male-biased effective sex ratio and recent step-by-step colonization in the bivalvePinctada mazatlanica
Authors: Arnaud-Haond S. , Monteforte M. , Blanc F. , Bonhomme F.
Published: December 2004

This paper presents a comparison of the geographical distribution of genetic variability at mitochondrial and nuclear loci among pearl oyster populations from the tropical American Pacific coast (Pinctada mazatlanica). Surprisingly, both mitochondrial and nuclear gene variability decreased regularly from north to south of the studied area, which, altogether with a significant correlation between genetic and geographical distances for mtDNA, suggests a recent colonization or re-colonization of the southern areas. However, the loss of diversity between north and south was much more important for mitochondrial than for nuclear DNA, and this did not translate into measurable fixation index at nuclear loci ( = 0.03, n.s.), contrary to the mitochondrial data ( = 0.18*). Smaller effective size of mtDNA accentuated by a strong male-biased effective sex ratio and step-by-step colonization from northern areas can explain this discrepancy among natural populations of this protandric species.