bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB
Authors: Ficko-Blean Elizabeth , Stubbs Keith A. , Nemirovsky Oksana , Vocadlo David J. , Boraston Alisdair B.
Published: April 2008

Mucopolysaccharidosis III (MPS III) has four forms (A–D) that result from buildup of an improperly degraded glycosaminoglycan in lysosomes. MPS IIIB is attributable to the decreased activity of a lysosomal α-
N
-acetylglucosaminidase (NAGLU). Here, we describe the structure, catalytic mechanism, and inhibition of
Cp
GH89 from
Clostridium perfringens
, a close bacterial homolog of NAGLU. The structure enables the generation of a homology model of NAGLU, an enzyme that has resisted structural studies despite having been studied for >20 years. This model reveals which mutations giving rise to MPS IIIB map to the active site and which map to regions distant from the active site. The identification of potent inhibitors of
Cp
GH89 and the structures of these inhibitors in complex with the enzyme suggest small-molecule candidates for use as chemical chaperones. These studies therefore illuminate the genetic basis of MPS IIIB, provide a clear biochemical rationale for the necessary sequential action of heparan-degrading enzymes, and open the door to the design and optimization of chemical chaperones for treating MPS IIIB.
Outer membrane protein G: Engineering a quiet pore for biosensing
Authors: Chen Min , Khalid Syma , Sansom Mark S. P. , Bayley Hagan
Published: April 2008

Bacterial outer membrane porins have a robust β-barrel structure and therefore show potential for use as stochastic sensors based on single-molecule detection. The monomeric porin OmpG is especially attractive compared with multisubunit proteins because appropriate modifications of the pore can be easily achieved by mutagenesis. However, the gating of OmpG causes transient current blockades in single-channel recordings that would interfere with analyte detection. To eliminate this spontaneous gating activity, we used molecular dynamics simulations to identify regions of OmpG implicated in the gating. Based on our findings, two approaches were used to enhance the stability of the open conformation by site-directed mutagenesis. First, the mobility of loop 6 was reduced by introducing a disulfide bond between the extracellular ends of strands β12 and β13. Second, the interstrand hydrogen bonding between strands β11 and β12 was optimized by deletion of residue D215. The OmpG porin with both stabilizing mutations exhibited a 95% reduction in gating activity. We used this mutant for the detection of adenosine diphosphate at the single-molecule level, after equipping the porin with a cyclodextrin molecular adapter, thereby demonstrating its potential for use in stochastic sensing applications.
Molecular mechanism of pH sensing in KcsA potassium channels
Authors: Thompson Ameer N. , Posson David J. , Parsa Pirooz V. , Nimigean Crina M.
Published: April 2008

The bacterial potassium channel KcsA is gated by high concentrations of intracellular protons, allowing the channel to open at pH < 5.5. Despite prior attempts to determine the mechanism responsible for pH gating, the proton sensor has remained elusive. We have constructed a KcsA channel mutant that remains open up to pH 9.0 by replacing key ionizable residues from the N and C termini of KcsA with residues mimicking their protonated counterparts with respect to charge. A series of individual and combined mutations were investigated by using single-channel recordings in lipid bilayers. We propose that these residues are the proton-binding sites and at neutral pH they form a complex network of inter- and intrasubunit salt bridges and hydrogen bonds near the bundle crossing that greatly stabilize the closed state. In our model, these residues change their ionization state at acidic pH, thereby disrupting this network, modifying the electrostatic landscape near the channel gate, and favoring channel opening.
Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance
Authors: Jayasooriya Anura P. , Mathai Michael L. , Walker Lesley L. , Begg Denovan P. , Denton Derek A. , Cameron-Smith David , Egan Gary F. , McKinley Michael J. , Rodger Paula D. , Sinclair Andrew J. , Wark John D. , Weisinger Harrison S. , Jois Mark , Weisinger Richard S.
Published: April 2008

In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE
−/−
) and compared with wild-type littermates. Compared with wild-type littermates, ACE
−/−
mice had lower body weight and a lower proportion of body fat, especially in the abdomen. ACE
−/−
mice had greater fed-state total energy expenditure (TEE) and resting energy expenditure (REE) than wild-type littermates. There were pronounced increases in gene expression of enzymes related to lipolysis and fatty acid oxidation (lipoprotein lipase, carnitine palmitoyl transferase, long-chain acetyl CoA dehydrogenase) in the liver of ACE
−/−
mice and also lower plasma leptin. In contrast, no differences were detected in daily food intake, activity, fed-state plasma lipids, or proportion of fat excreted in fecal matter. In conclusion, the reduction in ACE activity is associated with a decreased accumulation of body fat, especially in abdominal fat depots. The decreased body fat in ACE
−/−
mice is independent of food intake and appears to be due to a high energy expenditure related to increased metabolism of fatty acids in the liver, with the additional effect of increased glucose tolerance.
Breastfeeding in polycystic ovary syndrome
Authors: VANKY ESZTER , ISAKSEN HEGE , HAASE MOEN METTE , CARLSEN SVEN M.
Published: April 2008

Background. To investigate the breastfeeding rate in new mothers with polycystic ovary syndrome (PCOS). Methods. Case‐control study. Thirty‐six women with PCOS and 99 controls matched for age, gestational length and parity, answered a questionnaire. Breastfeeding at one‐, three‐ and six‐months postpartum was registered and the two groups were compared. In the women with PCOS, androgen levels through pregnancy were analysed and related to breastfeeding rate. Results. At one‐month postpartum, 27 (75%) of the women with PCOS were breastfeeding exclusively, whereas five (14%) did not breastfeed at all. Among controls, 88 (89%) were breastfeeding exclusively and two (2%) did not breastfeed (p = 0.001). At three‐ and six‐months postpartum, breastfeeding was equal in the two groups. Problems with sore nipples and seeking professional lactation support were also equal. Dehydroepiandrosterone‐sulphate levels at gestational week 32 and 36 showed a weak negative association with breastfeeding in PCOS women. Breastfeeding rate was not associated with maternal gestational levels of androstenedione, testosterone, sex‐hormone binding globulin, or free testosterone index in PCOS. Conclusions. Women with PCOS appear to have a reduced breastfeeding rate in the early postpartum period. Possibly, gestational dehydroepiandrosterone‐sulphate might negatively influence breastfeeding rate in women with the syndrome.
Yolk sac volume assessed by three‐dimensional ultrasonography using the VOCAL method
Authors: CRISTINE RÔLO LÍLIAM , MARCONDES MACHADO NARDOZZA LUCIANO , ARAUJO JÚNIOR EDWARD , MARTIN NOWAK PAULO , FERNANDES MORON ANTONIO
Published: April 2008

Objectives. Establish normative data for yolk sac volume (YSV) at 7–10 weeks of gestation assessed by transvaginal three‐dimensional ultrasonography (3D‐US) using the VOCAL method and analyze its correlation with gestational age (GA) and crown‐rump length (CRL). Methods. A cross‐sectional study involving 62 normal pregnancies was performed to assess YSV from 7 to 10 weeks of gestational age. An endocavitary volumetric transducer (3D5‐8EK) was used for all measurements. The VOCAL (Virtual Organ Computer‐aided AnaLysis) method with a 30° rotation angle was used for volumetric calculations. Regression models were constructed to analyze the correlation between YSV and GA or CRL The mean, standard deviation, median, minimum and maximum values were calculated for each gestational age. Results. There was a poor correlation between YSV and GA or CRL. The quadratic regression was the model that best expressed the correlation between these variables: R2 = 0.188 for GA and R2 = 0.203 for CRL. The mean YSV went from 0.063 cm3 (95% CI: 0.047; 0.080) at 7 weeks to 0.164 cm3 (95% CI 0.095; 0.232) at 10 weeks. Conclusion. Reference limits were generated for first trimester YSV using 3D‐US. There was a poor correlation between YSV and GA or CRL.
Complete destruction of urethra and bladder neck following symphysiotomy and results of attempted corrective surgery
Authors: ONSRUD MATHIAS , SJØVEIAN SOLBJØRG , MUKWEGE DENIS
Published: April 2008

Four (0.8%) out of 526 obstetric fistulas were related to a preceding symphysiotomy procedure. Complete destruction of the urethra and bladder neck with retropubic fibrosis was found. Faulty technique is the most probable cause. All women had stillborn babies before the symphysiotomy delivery, and tissue damage due to obstructed labor could have been a predisposing factor. A neo‐urethra was successfully constructed in three of the four women, but continence in standing position was not obtained.
Increasing incidence of anal sphincter tears among primiparas in Sweden: A population‐based register study
Authors: EKÉUS CECILIA , NILSSON EMMA , GOTTVALL KARIN
Published: April 2008

Background. The aim of this study was to examine the incidence and risk factors for anal sphincter tears (ASTs) at delivery. Methods. A national population‐based study was conducted with data from the Medical Birth Register including all primiparas with singleton pregnancy, who gave birth vaginally in Sweden from 1994 to 2004 (n = 365,886). Women with a third and fourth degree AST were compared with those who gave birth during the same period without incurring such tears. Results. The incidence of third degree AST increased by >60%, from 3.4% in 1994 to 5.2% in 2004 in spontaneous births, and from 8.7 to 14.8% in instrumental deliveries during the study period. The proportion of fourth degree AST increased from 0.3 to 0.55% in spontaneous births and from 0.8 to 1.4% in instrumental‐assisted deliveries during the same period. Compared with non‐instrumental delivery, vacuum extraction (VE) deliveries were related to an increased risk of AST. An infant birth weight of >4,000 g was also associated with an increased risk for both third and fourth degree AST. In addition, women born in Africa and Asia had significantly higher risk for both third and fourth degree AST compared to women born in Sweden. Conclusion. The incidence of third and fourth degree AST increased in both spontaneous births and instrumental deliveries. Instrumental delivery and an infant birth weight >4,000 g are the main risk factors for AST. Women from Africa and Asia have pronounced risks.
Italy's politics without policy: Balancing Atlanticism and Europeanism in the Middle East
Authors: Del Sarto Raffaella A. , Tocci Nathalie
Published: April 2008

Focusing on Italy's Middle East policies under the second Berlusconi (2001–2006) and the second Prodi (2006–2008) governments, this article assesses the manner and extent to which the observed foreign policy shifts between the two governments can be explained in terms of the rebalancing between a ‘Europeanist’ and a transatlantic orientation. Arguing that Rome's policy towards the Middle East hinges less on Italy's specific interests and objectives in the region and more on whether the preference of the government in power is to foster closer ties to the United States or concentrate on the European Union, the analysis highlights how these swings of the pendulum along the EU–US axis are inextricably linked to a number of underlying structural weaknesses of Rome's foreign policy. In particular, the oscillations can be explained by the prevalence of short-term political (and domestic) considerations and the absence of long-term, substantive political strategies, or, in short, by the phenomenon of ‘politics without policy’ that often characterises Italy's foreign policy.
Between ambition and ambivalence: Italy and the European Union's Mediterranean policy
Authors: Carbone Maurizio
Published: April 2008

This article reviews Italy's role in the various phases of the European Union's policy towards the Mediterranean: thead hocpolicy of the 1950s and 1960s, the Global Mediterranean Policy developed in the 1970s, the Euro-Mediterranean Partnership agreed in Barcelona in 1995, the European Neighbourhood Policy signed in 2003, the proposal launched by French president Nicolas Sarkozy in 2006 for a Mediterranean Union. The overall argument is that the various Italian governments have carried out an ambivalent and often reactive policy: on the one hand, they have consistently tried to promote a Mediterranean dimension in the European Union, though without upsetting the United States; on the other hand, they have limited the extension of trade privileges to exports from North Africa. While the end of the Cold War provided a new opportunity for Italy to play a more assertive role in the international arena, the two coalitions that have alternated in power have substantially failed to move the Mediterranean to the centre of Italy's and the European Union's external policy. A partial change of attitude – yet a reactive policy – emerged under the second Prodi Government, when Italy and Spain became close allies in an attempt to counter-balance the new activist policy of Sarkozy.
Italy and the Balkans: The rise of a reluctant middle power
Authors: Belloni Roberto , Morozzo della Rocca Roberto
Published: April 2008

Since the early 1990s Italy has been engaged in promoting peace and stability in the Balkans with a growing amount of political, economic and military resources. At the beginning of the process of Yugoslav dissolution, the Italian polity was torn apart by a set of political and financial scandals that prevented the development of an assertive foreign policy. Over time, however, Italy was able to play a more relevant and constructive role. This article traces Italy's policy towards the Balkans from its modest beginnings to the present day, focusing on four key political/economic events: the war in Bosnia, the Telekom Serbia affair, the war in Kosovo and the support given to the nascent Albanian democracy. Generally speaking, Italy has provided a positive, although modest, contribution to bringing peace and stability to the region.
Italy and European Union enlargement: A comparative analysis of left and right governments
Authors: Fossati Fabio
Published: April 2008

This article explores the attitudes of Italy's ruling and opposition parties towards the European Union (EU) enlargement process in Central and Eastern Europe. It shows that during both left (1996–2001) and right (2001–2006) governments there was a convergence between conservative and constructivist political platforms. In the first case, support for the Balkan countries (i.e., Slovenia, Romania, Bulgaria, Croatia) and Turkey was based on their economic (penetration of Italian firms) and political (stabilisation of a difficult area) potential. In the second case, support was justified for both economic (i.e., redistributive policy towards Romania, Bulgaria and Croatia) and cultural (i.e., pursuing a ‘plural’ Europe by including Turkey) reasons. Some liberal criticism based on Turkey's partial compliance with the political requirements for accession were raised by individual politicians of moderate right and left parties, and cultural biases against Islamic Turkey were stressed by the Lega Nord. Neither view, however, had a significant impact on the decision-making process.
Phonological awareness, reading accuracy and spelling ability of children with inconsistent phonological disorder
Authors: Holm Alison , Farrier Faith , Dodd Barbara
Published: April 2008

Background:Although children with speech disorder are at increased risk of literacy impairments, many learn to read and spell without difficulty. They are also a heterogeneous population in terms of the number and type of speech errors and their identified speech processing deficits. One problem lies in determining which preschool children with speech disorder will have difficulties acquiring literacy skills.

Aims:Two studies are presented that investigate the relationship between speech disorders and literacy. The first examined the phonological awareness abilities of children with different types of speech difficulties. The second study investigated the literacy skills of children with a history of inconsistent speech disorder.

Methods & Procedures:Experiment 1 measured the syllable segmentation, rhyme awareness and alliteration awareness of 61 preschool children: 46 with speech disorder (14 with delayed development, 17 who made consistent non‐developmental errors, and 15 who made inconsistent errors) and 15 typically developing controls. Experiment 2 assessed the reading accuracy, spelling and phonological awareness abilities of nine 7‐year‐old children with a history of inconsistent phonological errors.

Outcomes & Results:The first study indicated unexpected patterns of performance. While the Delayed group performed less well than controls on all tasks, the Consistent group showed poor performance on rhyme and alliteration but appropriate performance on syllable segmentation. The Inconsistent group performed most poorly on syllable segmentation but no differently from controls on the other two tasks. The second study indicated that children with a history of inconsistent phonological disorder performed no differently from controls on measures of phonological awareness and reading, but less well on measures of spelling ability.

Conclusions:The results support classification of speech disorders and show a differentiation of phonological awareness skills across groups. Children with consistent atypical speech errors have poor phonological awareness and are most at risk for literacy difficulties. Those with inconsistent phonological disorder are at increased risk of spelling difficulties. The findings indicate that phonological awareness and spelling skill are distinct processing systems and highlight the role of phonological assembly skills (i.e. storing and/or retrieving phonological output plans) in spelling output. The interactive processes between reading and spelling are discussed.
Investigating factors related to the effects of time‐out on stuttering in adults
Authors: Franklin Diane E. , Taylor Catherine L. , Hennessey Neville W. , Beilby Janet M.
Published: April 2008

Background: Response‐contingent time‐out has been shown to be an effective technique for enhancing fluency in people who stutter. However, the factors that determine individual responsiveness to time‐out are not well understood.

Aims: The study investigated the effectiveness of using response‐contingent time‐out to reduce stuttering frequency in adults who stutter. In addition, it investigated the predictive value of participants' stutter severity, age, previous treatment history, and type of stutter on the responsiveness to time‐out conditioning.

Methods & Procedures: Sixty people who stutter participated in the study. Half were exposed to time‐out following each moment of stuttering over a 40‐min period, the remaining participants acted as controls.

Outcomes & Results: Results showed that individuals who stutter are highly responsive to time‐out, and that the participants with a more severe stutter responded better than those with a mild stutter. To a lesser degree, previous treatment and speech rate also influenced treatment success. Age and type of stutter did not, although the proportion of repetition types of stutters increased over the experiment conditions, with prolongations and blocks decreasing, for the treatment group.

Conclusions: This simple operant conditioning treatment method is effective in reducing stuttering. Individuals respond to time‐out regardless of their age, type of stutter, stuttering severity or treatment history, thus it is a treatment methodology potentially suitable for all clients. This study investigated initial responsiveness to time‐out; therefore, further research is necessary to determine the durability of fluency over time.
Case study using ultrasound to treat //
Authors: Modha Geetanjalee , Bernhardt B. May , Church Robyn , Bacsfalvi Penelope
Published: April 2008

Background: Ultrasound has shown promise as visual feedback in remediation of //.

Aims: To compare treatment for // with and without ultrasound.

Methods & Procedures: A Canadian English‐speaking adolescent participated in a case study with a no treatment baseline, alternating treatment blocks with and without ultrasound and a final no treatment period.

Outcomes & Results: Formant values and trained listener ratings of speech samples indicated improvement in // production, particularly after the introduction of ultrasound.

Conclusions: Ultrasound appeared to facilitate the acquisition of // for the participant. Large‐scale studies are needed to evaluate ultrasound further.
Analysis of goalkeepers’ defence in the World Cup in Korea and Japan in 2002
Authors: Sainz De Baranda Pilar , Ortega Enrique , Palao José M.
Published: April 2008

The purpose of this study was to examine the characteristics of goalkeepers’ defence interventions in parallel with the type of opponent attack, the area of the last pass of attack, the shooting zone most often used, the body part most often used for the last pass or for shooting, and the technical and physical actions most often used for carrying out defensive technical skills. The sample consisted of 34 goalkeepers from the national teams that participated in 54 matches of the 2002 World Cup in Korea and Japan. The matches were analysed by systematic observation. A reliability kappa index of 0.95 was established between observers. The variables studied were: type of opponent attack, area of last pass of attack, field zone from which shot was taken, body part with which last part of attack or shot was made, zone of goalkeeper intervention, defensive technical and physical actions of goalkeeper intervention. Results related to opposing team's attacks showed that teams most often used positional attacks and the last pass came from the far zones. The foot was the body part most often used to finish the attack. Upon analysing the shots taken, we found that in relation to shooting angle, the central zones are the ones that are most utilized, and in relation to shooting distance, similar percentages were found in the zone outside the penalty area and the zone situated between the penalty area line and the goal area line. Results related to goalkeepers’ defence showed that the penalty area was the zone most often used, and the defensive actions most frequently used were the save, followed by foot control, and then the clear out. Our data provide reference values to adapt the training of goalkeepers to the characteristics of the competition.
The use of imagery across competitive levels and time of season: a cross‐sectional study among synchronized skaters in Finland
Authors: Arvinen‐Barrow Monna , Weigand Daniel A. , Hemmings Brian , Walley Malcolm
Published: April 2008

The purpose of this study was to gain an insight into the use of imagery by Finnish synchronized skaters. A total of 269 skaters (senior=85, junior=98, novice=86) simultaneously completed the original and a translated version of the Sport Imagery Questionnaire (SIQ; Hall, Mack, Paivio, & Hausenblas, 1998) twice, first at the beginning of the pre‐season (July–August 2002) and then during the competitive season (January 2003). Multivariate analyses of variance revealed (all P<0.05) that senior skaters used more cognitive specific (CS), motivational general‐arousal (MG‐A), and motivational general‐mastery (MG‐M) imagery than junior skaters; differences in CS, cognitive general (CG), MG‐A, and MG‐M imagery were found between senior and novice skaters; between junior and novice skaters, differences were found in CG and MG‐A imagery. Time of season analyses revealed skaters used more CG, MS, and MG‐M imagery during the competitive season than at the beginning of the pre‐season. No significant interaction effect between competitive level and time of season was observed. The results are discussed in relation to the applied model of imagery (Martin, Moritz, & Hall, 1999). To make competitive level transitions less demanding, the results suggest that a psychological skills training programme should be introduced for novice synchronized skaters.
Competitive experience and performance status: an investigation into multidimensional anxiety and coping
Authors: Hanton Sheldon , Neil Richard , Mellalieu Stephen D. , Fletcher David
Published: April 2008

In this study, we examined the influence of competitive experience (high vs. low) and performance status (current‐elite vs. past‐elite) upon athletes’ (N=217) multidimensional trait anxiety, self‐confidence, and coping responses. Significant interaction effects showed that the current‐elite group, with high experience, had the highest levels of self‐confidence and most facilitative interpretation of worry symptoms. Independent variable analysis revealed that the high‐experience group reported lower somatic anxiety levels than their low‐experience counterparts, and viewed the use of problem‐ and avoidance‐focused coping strategies as more and less effective respectively. Current‐elite performers reported lower worry intensity and more facilitative interpretations of somatic anxiety than the past‐elite performers, as well as the use of more effective problem‐focused and positive emotion‐focused coping. The findings highlight competitive experience and performance status as important variables in the study of multidimensional anxiety and coping.
Determination of body composition based on hydrostatic weighing without head submersion for Japanese young adults
Authors: Demura Shinichi , Yamaji Shunsuke , Yamada Takayoshi , Minami Masaki
Published: April 2008

The purpose of this study was to examine the accuracy and reliability of whole‐body volume, body density, and percent body fat calculated from body volume without the head (V NH), as assessed by hydrostatic weighing without head submersion and predicted head volume (pV H) based on head parameters, as compared with standard hydrostatic weighing. Participants comprised 29 males and 27 females aged 17–26 years. Head volume was predicted from anthropometric head parameters using a prediction equation. Underwater weights with/without head submersion were measured five times. The reliability of underwater weighing without head submersion was very good (intraclass correlation coefficient: males=0.998, females=0.998) as was that for traditional head submersion. The relationship between the sum of V NH and pV H and the whole‐body volume measured by hydrostatic weighing was very high (males=0.998, females=0.999), and their values were very similar with an error range of 300–400 ml. Although percent body fat assessed from the sum of V NH and pV H showed a slight scatter of 2–3% from the identity line of percent body fat assessed by hydrostatic weighing, the relationships for both sexes were very strong (males=0.918, females=0.957). The errors (2 standard deviations) as determined by Bland‐Altman plots between the two methods were −3.2 to 2.6% in males and −2.3 to 2.8% in females. There was no significant bias in percent body fat estimated by the two methods (hydrostatic weighing with/without head submersion), and the sum of V NH and pV H could validly estimate body composition, regardless of physical size. It is suggested that hydrostatic weighing without head submersion is a valid and convenient alternative technique.
Rac1 accumulates in the nucleus during the G2 phase of the cell cycle and promotes cell division
Authors: Michaelson David , Abidi Wasif , Guardavaccaro Daniele , Zhou Mo , Ahearn Ian , Pagano Michele , Philips Mark R.
Published: April 2008

Rac1 regulates a wide variety of cellular processes. The polybasic region of the Rac1 C terminus functions both as a plasma membrane–targeting motif and a nuclear localization sequence (NLS). We show that a triproline N-terminal to the polybasic region contributes to the NLS, which is cryptic in the sense that it is strongly inhibited by geranylgeranylation of the adjacent cysteine. Subcellular fractionation demonstrated endogenous Rac1 in the nucleus and Triton X-114 partition revealed that this pool is prenylated. Cell cycle–blocking agents, synchronization of cells stably expressing low levels of GFP-Rac1, and time-lapse microscopy of asynchronous cells revealed Rac1 accumulation in the nucleus in late G2 and exclusion in early G1. Although constitutively active Rac1 restricted to the cytoplasm inhibited cell division, activated Rac1 expressed constitutively in the nucleus increased the mitotic rate. These results show that Rac1 cycles in and out of the nucleus during the cell cycle and thereby plays a role in promoting cell division.
T cell receptor–instructed αβ versus γδ lineage commitment revealed by single-cell analysis
Authors: Kreslavsky Taras , Garbe Annette I. , Krueger Andreas , von Boehmer Harald
Published: April 2008

αβ and γδ T cell lineages develop in the thymus from a common precursor. It is unclear at which stage of development commitment to these lineages takes place and in which way T cell receptor signaling contributes to the process. Recently, it was demonstrated that strong TCR signals favor γδ lineage development, whereas weaker TCR signals promote αβ lineage fate. Two models have been proposed to explain these results. The first model suggests that commitment occurs after TCR expression and TCR signaling directly instructs lymphocytes to adopt one or the other lineage fate. The second model suggests that commitment occurs before TCR expression and that TCR signaling merely confirms the lineage choice. By tracing the fate of single T cell precursors, this study shows that there is no commitment to either the αβ or γδ lineage before TCR expression and that modulation of TCR signaling in progeny of a single TCR-expressing cell changes lineage commitment.
During negative selection, Nur77 family proteins translocate to mitochondria where they associate with Bcl-2 and expose its proapoptotic BH3 domain
Authors: Thompson Jennifer , Winoto Astar
Published: April 2008

Apoptosis accompanying negative selection is a central but poorly understood event in T cell development. The Nur77 nuclear steroid receptor and Bim, a proapoptotic BH3-only member of the Bcl-2 family, are two molecules implicated in this process. However, how they relate to each other and how Nur77 induces apoptosis remain unclear. In thymocytes, Nur77 has been shown to induce cell death through a transcriptional-dependent pathway, but in cancer cell lines, Nur77 was reported to induce apoptosis through conversion of Bcl-2 into a killer protein at the mitochondria. Whether this Nur77 transcriptional-independent pathway actually occurs in vivo remains controversial. Using an optimized fractionation protocol for thymocytes, here we report that stimulation of CD4+CD8+ thymocytes results in translocation of Nur77 and its family member Nor-1 to the mitochondria, leading to their association with Bcl-2 and exposure of the Bcl-2 proapoptotic BH3 domain. In two T cell receptor transgenic models of negative selection, F5 and HY, a conformational change of the Bcl-2 molecule in the negatively selected T cell population was similarly observed. Thus, the Nur77 family and Bim pathways converge at mitochondria to mediate negative selection.
Positive selection drives a correlation between non-synonymous/synonymous divergence and functional divergence
Authors: Tennessen Jacob A.
Published: April 2008

Motivation: Functional divergence among proteins is often assumed to be strongly influenced by natural selection, as inferred from the ratio of non-synonymous nucleotide divergence (dN) to synonymous nucleotide divergence (dS). That is, the more a mutation changes protein function, the more likely it is to be either selected against or selectively favored, and because the dN/dS ratio is a measure of natural selection, this ratio can be used to predict the degree of functional divergence (dF). However, these hypotheses have rarely been experimentally tested.

Results: I present a novel method to address this issue, and demonstrate that divergence in bacteria-killing activity among animal antimicrobial peptides is positively correlated with the log of the dN/dS ratio. The primary cause of this pattern appears to be that positively selected substitutions change protein function more than neutral substitutions do. Thus, the dN/dS ratio is an accurate estimator of adaptive functional divergence.

Contact:  tennessj@science.oregonstate.edu

Supplementary information:  Supplementary data, including GenBank Accession numbers, are available at Bioinformatics online.
Adaptive dynamics with a single two-state protein
Authors: Csikász-Nagy Attila , Soyer Orkun S
Published: April 2008

An important step towards understanding biological systems is to relate simple biochemical elements to dynamics. Here, we present the arguably simplest dynamical element in biochemical networks. It consists of a single protein with two states (active and inactive) and an external signal that catalyses the conversion between these two states. Further, there is steady synthesis and degradation of the inactive and active forms, respectively. As this element captures both structural and dynamical features of biochemical networks at the lowest level, we refer to it as a biochemical network unit (BioNetUnit). Using both simulations and mathematical analysis, we find that BioNetUnit shows perfect adaptation that leads to temporal responses to step changes in the incoming signal. Compared with a well-described adaptive system, which is found in bacterial chemotaxis, BioNetUnit has lower sensitivity and its adaptation time is less robust to the base signal levels. We show that these dynamical limitations lead to ‘once-and-only-once’ responses for certain signal sequences. These findings demonstrate that BioNetUnit is relevant in adaptive and cyclic processes. In particular, it could be seen as a generic representation for ligand-activated receptors that are desensitized upon continuous activation. The analysis of coupled BioNetUnits will show how the presented dynamics at single unit will change upon increased system complexity and how such systems would mediate biological functions.
Stochastic theories for the irregularity of ENSO
Authors: Kleeman Richard
Published: April 2008

The El Niño/Southern Oscillation (ENSO) phenomenon is the dominant climatic fluctuation on interannual time scales. It is an irregular oscillation with a distinctive broadband spectrum. In this article, we discuss recent theories that seek to explain this irregularity. Particular attention is paid to explanations that involve the stochastic forcing of the slow ocean modes by fast atmospheric transients. We present a theoretical framework for analysing this picture of the irregularity and also discuss the results from a number of coupled ocean–atmosphere models. Finally, we briefly review the implications of the various explanations of ENSO irregularity to attempts to predict this economically significant phenomenon.
Structural basis of histone H4 recognition by p55
Authors: Song Ji-Joon , Garlick Joseph D. , Kingston Robert E.
Published: April 2008

p55 is a common component of many chromatin-modifying complexes and has been shown to bind to histones. Here, we present a crystal structure of Drosophila p55 bound to a histone H4 peptide. p55, a predicted WD40 repeat protein, recognizes the first helix of histone H4 via a binding pocket located on the side of a β-propeller structure. The pocket cannot accommodate the histone fold of H4, which must be altered to allow p55 binding. Reconstitution experiments show that the binding pocket is important to the function of p55-containing complexes. These data demonstrate that WD40 repeat proteins use various surfaces to direct the modification of histones.
Telomere length and the risk of lung cancer
Authors: Jang Jin Sung , Choi Yi Young , Lee Won Kee , Choi Jin Eun , Cha Sung Ick , Kim Yeon Jae , Kim Chang Ho , Kam Sin , Jung Tae Hoon , Park Jae Yong
Published: April 2008

Telomeres play a key role in the maintenance of chromosome integrity and stability. There is growing evidence that short telomeres induce chromosome instability and thereby promote the development of cancer. We investigated the association of telomere length and the risk of lung cancer. Relative telomere length in peripheral blood lymphocytes was measured by quantitative polymerase chain reaction in 243 lung cancer patients and 243 healthy controls that were frequency‐matched for age, sex and smoking status. Telomere length was significantly shorter in lung cancer patients than in controls (mean ± standard deviation: 1.59 ± 0.75versus2.16 ± 1.10,P < 0.0001). When the subjects were categorized into quartiles based on telomere length, the risk of lung cancer was found to increase as telomere length shortened (Ptrend< 0.0001). In addition, when the median of telomere length was used as the cutoff between long and short telomeres, individuals with short telomeres were at a significantly higher risk of lung cancer than those with long telomeres (adjusted odds ratio = 3.15, 95% confidence interval = 2.12–4.67,P < 0.0001). When the cases were categorized by tumor histology, the effect of short telomere length on the risk of lung cancer was more pronounced in patients with small cell carcinoma than in those with squamous cell carcinoma and adenocarcinoma (P = 0.001, test for homogeneity). These findings suggest that shortening of the telomeres may be a risk factor for lung cancer, and therefore, the presence of shortened telomeres may be used as a marker for susceptibility to lung cancer. (Cancer Sci2008; 99: 1385–1389)
OBSERVATIONS ON EAST AFRICAN BIRDS OF PREY
Authors: Brown L. H.
Published: April 2008

Summary

East Africa is a country very rich in birds of prey, both resident and migrant, partly because a majority of migrant Eurasian birds of prey enter Africa through Suez in winter. Diurnal birds of prey are both more numerous and more varied than nocturnal, especially among migrant species.

The size range of birds of prey, both diurnal and nocturnal, in East Africa is nearly equivalent to that occurring in the whole world. The predator‐prey relationship is thus exceedingly complex in East Africa.

Diurnal birds of prey hunt by sight and nocturnal by the use of sight and hearing. Diurnal birds of prey can thus make use of both live and dead prey, but owls are only able to capture living prey and do not feed upon carrion.

Almost all animals in East Africa, from elephants to small insects, are either eaten as carrion or preyed upon as live prey by some species of raptor. Most live animals in the size range from small insects to animals 5 kg in weight are preyed upon by a diurnal or a nocturnal bird of prey at some stage of the twenty‐four hours. Carrion is not consumed by birds of prey at night.

Comparison of the raptor avi‐fauna of forests with that in savannah indicates that in forests raptors are much less likely to eat carrion than in open country, but that the size range of raptors preying upon live animals is much the same in forests and in open country. Nocturnal birds of prey are less successful in a forest environment than are diurnal species.

The possible effect of individual species (Aquila wahlbergi and Polemaetus bellicosus) and of a combination of many species on the possible population of animals in home ranges of known size is discussed. It is concluded that there is no evidence that either an individual species or a combination of several could effectively limit the populations of certain prey species.

Concentrations of several breeding pairs of large raptors in apparent association with one another are mentioned. The interrelations of such species, and the effects of possible competition between members of such associations, are discussed. It is concluded that real competition is likely to be slight and that such groups of nesting raptors must be due to a form of inter‐specific gregariousness.
ANIMAL HUSBANDRY RESEARCH AND WILDLIFE IN EAST AFRICA
Authors: Ledger H. P.
Published: April 2008

Summary

It is only in recent years that there has been an appreciation that the problems of wildlife and domestic animal husbandry are complementary and form an integral part of the overall problem of land use.

To investigate the meat production potential of East African ruminants a standard form of body and carcase dissection analysis has been devised and is described in detail.

It is hoped that a better knowledge of the physiological adaption to their environment of some of the wild species may help to indicate methods of improving animal husbandry in the dry tropics. The data obtained during the course of these investigations will also provide information as to the meat production potential of the individual species.

The lines of thought engendered by these investigations are discussed.
SOME PRELIMINARY OBSERVATIONS ON THE FOOD OF ELEPHANT IN THE TSAVO ROYAL NATIONAL PARK (EAST) OF KENYA
Authors: Bax P. Napier , Sheldrick D. L. W.
Published: April 2008

Summary

The background to this study is discussed. In the last five years elephant have caused a change in vegetation from dense bush to open country over large regions near the permanent water supplies in the Tsavo Royal National Park (East) of Kenya. Much destruction has also been caused, or aggravated, by fire. (See Map 1).

In the 1961 drought, rhinoceros appeared to have suffered from competition with elephant for food, to the point of starvation, but there did not seem to be serious competition in normal dry seasons, such as 1962. In the drought the destruction of trees and bushes by elephant occurred to a far greater extent than during the dry season of 1962.

The records of plants eaten apply specifically only to the areas where the data were collected (see Map 2), but probably in a more general manner to the Park as a whole. These plants, with their observed relative importance, are listed in Appendix I. It is emphasised that this study is as yet only in a preliminary stage, and should continue for several years, before final conclusions can be drawn.

Elephant were found to eat a few plants in bulk at a particular time, such as grasses, creepers and herbs, along with smaller quantities of other materiai such as bark and leaves. Grasses were always of varying importance. Bark and leaves formed a larger proportion of the food in the dry season than in the rains, but were always eaten to some degree. The plant species of which the feeds were composed varied seasonally and annually. Certain apparently suitable plants were not eaten.

Many food plants were analysed, and a few of these results are briefly mentioned. It appears possible that the eating of bark is a search for calcium, as the barks consumed are very rich in this mineral. Feeding behaviour is briefly described.
ECOLOGICAL SEPARATION OF THE LARGE MAMMAL SPECIES IN THE TARANGIRE GAME RESERVE, TANGANYIKA1
Authors: Lamprey H. F.
Published: April 2008

Summary

The ecological separation of 14 common ungulate species living in close contact with each other in a Tanganyika game reserve is shown to be achieved by six different factors:

1. the occupation of different vegetation types and broad habitats;

2. the selection of different types of food;

3. the occupation of different areas at the same season;

4. the occupation of the same area at different seasons;

5. the use of different feeding levels in the vegetation;

6. the occupation of different dry season refuges in the Masai area when the competition for food is greatest (zebra and wildebeest).

Habitat preferences are indicated by the frequency distribution of each species along the central of three 8,000 yard parallel transect paths which were traversed nearly daily for four years. Characteristic patterns of frequency are apparent for each of the species in the vegetation zones represented in the transect area. Certain species show a tendency, sometimes strong, to concentrate along the boundaries between adjoining vegetation zones and in the ecotones between the zones. This is ascribed to a greater diversity of food, availability of shelter from the sun and/or greater protection from predators.

Records of the animal species eating particular plant species are shown and (qualified in the light of other observations) used to deduce food preferences. The species are classified broadly into grass‐eaters, browsers and mixed feeders (grass and browse). In the case of the three common grass‐eaters, buffalo, wildebeest and zebra, a percentage analysis of the grass species eaten indicates that little differential preference is shown but that they take the palatable grasses largely in proportion to the frequency in which they occur in the habitats most used by the ungulate concerned. Buffalo are separated by their preference for denser vegetation. Wildebeest and zebra largely overlap ecologically in all respects except that the bulk of the populations of each species move to different dry season areas. Those species which are able to live without drinking free water, notably impala and Grant's gazelle, are able to make use of wild areas of waterless country when the animals requiring water are forced to move into dry season concentration areas near water.

The influence of the animals on the habitats and on other species is discussed and instances are given of species helping to shape the habitat to the advantage of both themselves and other species. Elephants are the main habitat modifiers and their capacity to improve water supplies and change the vegetation, and their facilitation of the feeding of other species is described. The formation of mixed herds is interpreted as being protective to one or both species concerned and is a further important facilitation. Little or no hindrance of one ungulate species by another was seen although herbivores show antagonistic behaviour towards carnivores smaller than themselves.
A CONTRIBUTION TO THE NATURAL HISTORY OF THE SPOTTED‐NECKED OTTER (LUTRA MACULICOLLIS LICHTENSTEIN) IN TANGANYIKA
Authors: Procter John
Published: April 2008

Summary

The Spotted‐necked Otter (Lutra maculicollis Lichtenstein), locally common in northwestern and south‐western Tanganyika, was not listed in the country's fauna until 1951. There is no previous literature about the otter in Tanganyika, and very little about it in other parts of Africa, although it is widely distributed south of Lat. 10° N., and common in Lake Victoria, where this study was made. It is a typical otter, weighing under 20 lbs., and reaching just over three feet overall. Sexes are rarely distinguishable in the field. The amount of white coloration varies from practically none to nearly the whole underside. Eyesight is poor but scent and hearing are moderately acute. Four kinds of call were noted. It is predominantly a lake‐dweller and spends almost all its waking life in the water, being comparatively clumsy on land. Most otters seen were in parties of four to six individuals and all move about considerably, although there is no true migration. Swimming otters use mainly the hind feet and dives normally last 15 seconds. Urination and defaecation take place on land and much time is spent basking and grooming. The main food is small fish but larger fish and some molluscs and crustaceans are also eaten. Otters are diurnal and the main fishing period is soon after dawn. The breeding cycle may be as follows: July—mating; September—young born; November—young taught to swim and fish; January—family parties moving about. Main enemies are man and probably crocodiles. Otters do not appear to have an adverse effect on the fishing industry.