bluuebunny/crossref_metadata_2025 huggingface dataset:
The development and introduction of entrustable professional activities at 2 community-based chiropractic student preceptorship sites in the United States
Authors: Gliedt Jordan A. , Mathers Kevin S. , King Jeff , Schneider Michael J. , Wiles Michael R.
Published: April 2024

Objective

Entrustable professional activities (EPAs) have seen widespread adoption in medical education and other health professions education. EPAs aim to provide a bridge between competency-based education and clinical practice by translating competencies into fundamental profession-specific tasks associated with clinical practice. Despite the extensive use of EPAs in health professions education, EPAs have yet to be introduced into chiropractic education. The purpose of this paper is to describe the development and introduction of EPAs as part of 2 community-based chiropractic student preceptorship education programs in the United States.

Methods

EPAs were developed and introduced at 2 community-based chiropractic preceptorship sites in 5 distinct steps: (1) differentiating EPAs from competencies, learning objectives, and knowledge, skills, and attitudes; (2) identifying EPAs; (3) mapping EPAs to competencies and necessary experience, knowledge, and skills; (4) designing EPA assessment strategies; and (5) implementing the use of EPAs.

Results

A total of 13 individual EPAs were developed and mapped to Council on Chiropractic Education meta-competency outcomes and underlying experience, knowledge, and skills. Three assessment tools were created to evaluate student entrustability for EPAs and enhance student self-assessment. The EPAs and assessment tools were integrated into chiropractic student preceptorships at each site.

Conclusion

This paper describes the development and introduction of EPAs at 2 community-based chiropractic preceptorship sites. Future research is needed to develop and standardize EPA use and assessment, and to evaluate outcomes associated with EPA use.
Assessing the Quality and Potential of Fried Noodles: An Analysis of Wheat and Afzelia africana Flour Blends in Chemical, Functional, Physical, and Sensory Dimensions
Authors: Emojorho Ernest Eguono , Reuben-Okoye Marian , Aphiar Agnes , Nwosu Adaora Ngozi , Anene Maryann Nkemakonam , Avbundiogba Eseoghene , Ochimana Titus Onucheojo , Ekpekpo Lauretta D.
Published: April 2024

Afzelia africana flour was produced by roasting, dehaulling and grinding seeds into flour. In this study, the chemical composition, functional, physical properties and sensory characteristics of fried noodles produced from wheat and Afzelia africana (Akpalata) flour blends were evaluated. Wheat   and Afzelia africana flours was blended in the ratio of 100:0(WFO), 95:5(WFAA1), 90:10(WFAA2), 85:15(WFAA3) and 80:20(WFAA4) as 100% wheat flour was used as the control. Samples were used to produce fried noodles. The functional qualities of flour mixes were examined. The noodles samples underwent physical, chemical, and sensory investigation. The noodle sample was cooked and sensory evaluation carried out. Result of proximate composition of the noodles ranged from (crude protein; 23.00- 30.05 crude fat; 10.00- 14.7%, ash; 0.95- 3.00%, crude fibre; 1.10- 2.95%, moisture; 7.50-9.00%, and carbohydrate; 50.00-53.11%) respectively. Functional results showed 0.64 to 0.66 g/cm3, 14.00 to 20.00 % oil absorption capacity, 25.20 to 36.50 ml swelling capacity and 21.00 to 25.90 % water absorption capacity. Physical properties results showed 11.65 – 12.75 cm length and 0.26 – 0.43 cm. The sensory scores showed that sample WFAA4 (80:20) was the most overall acceptable by the judges. In conclusion, acceptable noodles with improved protein content and reduce processing cost can be produced from blends of wheat and Afzelia africana flours.
Ingrown Toenail Management Across Mental Health and Other Health Facilities in Nigeria: A Review of Anesthetic and Surgical Management
Authors: Nwobu David Chibututu , Ezema Evaristus Chino , Okoye Tricia , Ugwu Amogechukwu Onyinye , Agazie Ogochukwu , Oranusi Ifeatu Ogochukwu , Hilkiah Eliakim , Chiebuka Emmanuel , Mmadubuchi John , Aleke Chinenye Loveth
Published: April 2024

Background: The management of ingrown toenails in Nigeria is notably underdeveloped, posing potential challenges for patients in mental health facilities and beyond. Addressing this issue requires an interdisciplinary approach and collaboration with other healthcare professionals. Furthermore, there is an important need for a comprehensive review of the treatment guidelines for the anesthetic and surgical techniques utilized in its treatment to improve the quality of patient care.
Methods: We employed a structured narrative approach to identify and review available articles on ingrown toenail management in mental health and other health facilities in Nigeria. We aimed to evaluate the anesthetic and surgical techniques utilized in managing these patients.
Results: No documented treatment for ingrown toenails was identified among patients in mental health facilities across Nigeria. While various surgical techniques are employed for management in other health facilities, the specific anesthesia techniques utilized are unclear.
Conclusions: A unified management protocol and guideline for ingrown toenails and developing podiatry training in Nigeria are imperative. Developing and implementing an effective treatment protocol improves the quality of care and widens coverage for all patients. In addition, establishing podiatry training across educational facilities could bridge this gap in ensuring optimal care for these patient populations.
Determinants of Survival and Prognostic Factors in Patients with Prostate Cancer: A Retrospective Analysis (2009-2018)
Authors: Freitas Carla Simone Moreira de , Souza Amanda Damasceno de , Rocha-Silva Fabiana , Marques-Silva Thaís Almeida , Soares Aleida Nazareth
Published: April 2024

Objective: To evaluate prognostic factors and survival determinants of patients with prostate cancer (PC) admitted to an oncology hospital.
Methods: Retrospective cohort study on 3,450 medical records of patients undergoing cancer treatment from 2009 to 2018, with follow-up until 2020, at the Center for High Complexity in Oncology (CACON), Muriaé, Minas Gerais, Brazil. Overall survival was estimated using the Kaplan-Meier method. For paired comparisons, the log-rank test was used. For multivariate analysis, the Cox Proportional Hazards method.
Results: From 2009 to 2018, 3,450 patients with PC were identified; the predominant profile of multiracial men (45.9%), with an average age of 72 years, no family history of cancer (39.6%), clinical stage II (57.70%), low Gleason score <=6 (52 .7%) and PSA level <10 ng/ml (40.9%). The probability of survival was estimated at 36, 48, and 60 months. Longer survival was found in men aged <60 - 36 (95% CI: 97); 48 (95% CI: 96); 60 (95% CI: 96). Gleason score: <=6 - 36 (95% CI: 98); 48 (95% CI: 97); 60 (95% CI: 96). Stage I: 36 (95% CI: 99); 48 (95% CI: 99); 60 (95% CI: 99). Initial treatment – Radiotherapy: 36 (95% CI: 97); 48 (95% CI: 96); 60 (95% CI: 96). PSA: <10 (ng/ml) 36 (95% CI: 99); 48 (95% CI: 98); 60 (95% CI: 98).
Conclusion: The individuals evaluated in this study had survival rates at 60 months higher than those observed in the national and world average for PC and prognostic factors, age >70 years, stage III and IV, elevated Gleason, and PSA >10 ng/ml. The results allow the use of new early diagnosis and treatment measures in the public network – Unified Health System (SUS), as well as proposing new control strategies and health promotion actions, aiming to reduce the morbidity and mortality of patients with PC.
Assessment of Genetic Diversity in Indian Mustard (Brassica juncea L. Czern & Coss) Genotypes Using D2 Analysis
Authors: Kumar Shubham , Kumar Mukesh , Tiwari Mayank , Chauhan Rahul Singh , Gurjar Trayambak
Published: April 2024

A total 44 varied genotypes of Indian mustard were assessed for Genetic divergence during the 2021-22 Rabi season, using a randomized complete block design (RCBD) comprising 3 replications. Fourteen distinct characteristics, including days to 50% flowering, days of maturity, plant height, No. of primary and secondary branches/ plant, pod length, No. of pod on main shoot, length of main shoot, No. of seeds per pod, test weight, B.Y, H.I, oil content and grain yield were observed. D2 values employed to classify the genotypes into seven clusters, with largest cluster being cluster II, comprising 10 genotypes. Cluster III exhibited maximum intra-cluster distance, while most significant inter-cluster distance was observed between cluster II and IV. This suggested that genotypes in cluster II possess a broad range of genetic diversity. Notably, days to maturity played a crucial role in contributing to Genetic divergence among the traits studied.
Effects of Dehydrated Cupuaçu Almond Bran Inclusion on Fermentation Profile and Bromatological Composition of Pennisetum purpureum Grass Silage
Authors: Rocha Jefferson Gomes da , Miranda Emerson Silva , Caldeira Flávio Henrique Bravim , Ciríaco Abílio da Paixão , Mesquita Alan Andrade , Reis Rafael Henrique Pereira dos , Cabral Luciano da Silva , Negrão Fagton de Mattos
Published: April 2024

This study aimed to evaluate the fermentative characteristics and the bromatological composition of elephant grass silages by adding dehydrated almonds of cupuaçu. A completely randomized design was used with four treatments (0, 15, 30, and 45%) and five replications. The variables analyzed were pH, effluent losses and dry matter recovery, dry matter, crude protein, neutral detergent fiber, acid detergent fiber, and hemicellulose. The data were submitted for analysis of variance and regression to the level of 5% probability using the statistical package SISVAR®. With the inclusion of dehydrated cupuaçu almonds was observed a linear increase (P<0.05) of 0.05, 1.14, 0.63, 2.43, and 2.52 percentage units for each percentage on pH, dry matter recovery, dry matter, neutral detergent fiber, and hemicellulose. On the other hand, for each 1% of the additive added was observed reduction of 0.20, 1.15, 0.035, 0.8, 0.38, and 0.36 for N-NH3, buffering power, effluents, gas loss, crude protein, and acid detergent fiber, respectively. The addition of dehydrated cupuaçu almonds to elephant grass silage promotes improvements in the silage composition; however, the amount to be added must be moderated as this additive increases the ph and the amount of fiber in the silage.
Essential fatty acid profiling for routine nutritional assessment unmasks adrenoleukodystrophy in an infant with isovaleric acidaemia
Authors: Bonilla Guerrero R. , Wolfe L. A. , Payne N. , Tortorelli S. , Matern D. , Rinaldo P. , Gavrilov D. , Melan M. , He M. , Steinberg S. J. , Raymond G. V. , Vockley J. , Gibson K. M.
Published: December 2008

We report a 16‐month‐old asymptomatic male with enzyme confirmed isovaleric acidaemia (IVA; isovaleryl‐CoA dehydrogenase deficiency; OMIM 243500) who, upon routine nutritional follow‐up, presented evidence of peroxisomal dysfunction. The newborn screen (2 days of life) revealed elevated C5‐carnitine (2.95 μmol/L; cutoff <0.09 μmol/L) and IVA was subsequently confirmed by metabolic profiling and in vitro enzymology. Plasma essential fatty acid (EFA) analysis, assessed to evaluate nutritional status during protein restriction and l‐carnitine supplementation, revealed elevated C26:0 (5.0 μmol/L; normal <1.3). Subsequently, metabolic profiling and molecular genetic analysis confirmed X‐linked adrenoleukodystrophy (XALD). Identification of co‐inherited XALD with IVA in this currently asymptomatic patient holds significant treatment ramifications for the proband prior to the onset of neurological sequelae, and critically important counselling implications for this family.
A demand model for international freight transport by road
Authors: Nuzzolo Agostino , Crisalli Umberto , Comi Antonio
Published: December 2008

This paper presents a system of models for the estimation of road international (import/export) freight flows by using a partial share approach. It allows to simulate generation (for export), attraction (for import) and distribution steps for the estimation of freight flows in quantities (commodity approach), from which the conversion in vehicles is made by using vehicle loading models. This modelling system has been specified according to an easy-to-use philosophy (suitable to be used for forecasting) by using aggregate variables, such as GDP. The calibration has been carried out by using a set of available data in Italy that allowed us to consider import/export flows by road for three different freight types (perishable, industrial and consumption goods).
Molecular basis for the substrate specificity of plant guanine nucleotide exchange factors for ROP
Authors: Fricke Inka , Berken Antje
Published: December 2008

Plant G proteins of the ROP/RAC family regulate cellular processes including cytoskeletal rearrangement in polar growth. Activation of the ROP molecular switch is triggered by guanine nucleotide exchange factors. Plant‐specific RopGEFs are exclusively active on ROPs despite their high homology to animal Rho proteins. Based on a sequence comparison of ROPs vs. animal Rho proteins together with structural data on distinct ROPs, we identified unique substrate determinants of RopGEF specificity by mutational analysis: asparagine 68 next to switch II, arginine 76 of a putative phosphorylation motif and the Rho insert are essential for substrate recognition by RopGEFs. These data also provide first evidence for a function of the Rho insert in interactions with GEFs.
Vectorial proton transfer coupled to reduction of O
2
and NO by a heme-copper oxidase
Authors: Huang Yafei , Reimann Joachim , Lepp Håkan , Drici Nadjia , Ädelroth Pia
Published: December 2008

The heme-copper oxidase (HCuO) superfamily consists of integral membrane proteins that catalyze the reduction of either oxygen or nitric oxide. The HCuOs that reduce O
2
to H
2
O couple this reaction to the generation of a transmembrane proton gradient by using electrons and protons from opposite sides of the membrane and by pumping protons from inside the cell or organelle to the outside. The bacterial NO-reductases (NOR) reduce NO to N
2
O (2NO + 2e
−
+ 2H
+
→ N
2
O + H
2
O), a reaction as exergonic as that with O
2
. Yet, in NOR both electrons and protons are taken from the outside periplasmic solution, thus not conserving the free energy available. The
cbb
3
-type HCuOs catalyze reduction of both O
2
and NO. Here, we have investigated energy conservation in the
Rhodobacter sphaeroides cbb
3
oxidase during reduction of either O
2
or NO. Whereas O
2
reduction is coupled to buildup of a substantial electrochemical gradient across the membrane, NO reduction is not. This means that although the
cbb
3
oxidase has all of the structural elements for uptake of substrate protons from the inside, as well as for proton pumping, during NO reduction no pumping occurs and we suggest a scenario where substrate protons are derived from the outside solution. This would occur by a reversal of the proton pathway normally used for release of pumped protons. The consequences of our results for the general pumping mechanism in all HCuOs are discussed.
Recognition and repair of UV lesions in loop structures of duplex DNA by DASH-type cryptochrome
Authors: Pokorny Richard , Klar Tobias , Hennecke Ulrich , Carell Thomas , Batschauer Alfred , Essen Lars-Oliver
Published: December 2008

DNA photolyases and cryptochromes (cry) form a family of flavoproteins that use light energy in the blue/UV-A region for the repair of UV-induced DNA lesions or for signaling, respectively. Very recently, it was shown that members of the DASH cryptochrome subclade repair specifically cyclobutane pyrimidine dimers (CPDs) in UV-damaged single-stranded DNA. Here, we report the crystal structure of
Arabidopsis
cryptochrome 3 with an in-situ-repaired CPD substrate in single-stranded DNA. The structure shows a binding mode similar to that of conventional DNA photolyases. Furthermore, CPD lesions in double-stranded DNA are bound and repaired with similar efficiency as in single-stranded DNA if the CPD lesion is present in a loop structure. Together, these data reveal that DASH cryptochromes catalyze light-driven DNA repair like conventional photolyases but lack an efficient flipping mechanism for interaction with CPD lesions within duplex DNA.
A selective Gβγ-linked intracellular mechanism for modulation of a ligand-gated ion channel by ethanol
Authors: Yevenes Gonzalo E. , Moraga-Cid Gustavo , Peoples Robert W. , Schmalzing Günther , Aguayo Luis G.
Published: December 2008

The current understanding about ethanol effects on the ligand-gated ion channel (LGIC) superfamily has been restricted to identify potential binding sites within transmembrane (TM) domains in the Cys-loop family. Here, we demonstrate a key role of the TM3–4 intracellular loop and Gβγ signaling for potentiation of glycine receptors (GlyRs) by ethanol. We discovered 2 motifs within the large intracellular loop of the GlyR α1subunit that are critical for the actions of pharmacological concentrations of ethanol. Significantly, the sites were ethanol-specific because they did not alter the sensitivity to general anesthetics, neurosteroids, or longern-alcohols. Furthermore, Gβγ scavengers selectively attenuated the ethanol effects on recombinant and native neuronal GlyRs. These results show a selective mechanism for low-ethanol concentration effects on the GlyR and provide a mechanism on ethanol pharmacology, which may be applicable to other LGIC members. Moreover, these data provide an opportunity to develop new genetically modified animal models and novel drugs to treat alcohol-related medical concerns.
The RNA binding protein CPEB regulates dendrite morphogenesis and neuronal circuit assembly in vivo
Authors: Bestman Jennifer E. , Cline Hollis T.
Published: December 2008

Visual system development requires experience-dependent mechanisms that regulate neuronal structure and function, including dendritic arbor growth, synapse formation, and stabilization. Although RNA binding proteins have been shown to affect some forms of synaptic plasticity in adult animals, their role in the development of neuronal structure and functional circuitry is not clear. Using two-photon time-lapse in vivo imaging and electrophysiology combined with morpholino-mediated knockdown and expression of functional deletion mutants, we demonstrate that the mRNA binding protein, cytoplasmic polyadenylation element binding protein1 (CPEB1), affects experience-dependent neuronal development and circuit formation in the visual system of
Xenopus laevis
. These data indicate that sensory experience controls circuit development by regulating translational activity of mRNAs.
A type II NAD(P)H dehydrogenase mediates light-independent plastoquinone reduction in the chloroplast of
Chlamydomonas
Authors: Jans Frédéric , Mignolet Emmanuel , Houyoux Pierre-Alain , Cardol Pierre , Ghysels Bart , Cuiné Stéphan , Cournac Laurent , Peltier Gilles , Remacle Claire , Franck Fabrice
Published: December 2008

In photosynthetic eukaryotes, nonphotochemical plastoquinone (PQ) reduction is important for the regulation of photosynthetic electron flow. In green microalgae where this process has been demonstrated, the chloroplastic enzyme that catalyses nonphotochemical PQ reduction has not been identified yet. Here, we show by an RNA interference (RNAi) approach that the
NDA2
gene, belonging to a type II NAD(P)H dehydrogenases family in the green microalga
Chlamydomonas reinhardtii
, encodes a chloroplastic dehydrogenase that functions to reduce PQ nonphotochemically in this alga. Using a specific antibody, we show that the Nda2 protein is localized in chloroplasts of wild-type cells and is absent in two Nda2-RNAi cell lines. In both mutant cell lines, nonphotochemical PQ reduction is severely affected, as indicated by altered chlorophyll fluorescence transients after saturating illumination. Compared with wild type, change in light excitation distribution between photosystems (‘state transition’) upon inhibition of mitochondrial electron transport is strongly impaired in transformed cells because of inefficient PQ reduction. Furthermore, the amount of hydrogen produced by Nda2-RNAi cells under sulfur deprivation is substantially decreased compared with wild type, which supports previous assumptions that endogenous substrates serve as source of electrons for hydrogen formation. These results demonstrate the importance of Nda2 for nonphotochemical PQ reduction and associated processes in
C. reinhardtii
.
Fluorescence detection of the movement of single KcsA subunits reveals cooperativity
Authors: Blunck Rikard , McGuire Hugo , Hyde H. Clark , Bezanilla Francisco
Published: December 2008

The prokaryotic KcsA channel is gated at the helical bundle crossing by intracellular protons and inactivates at the extracellular selectivity filter. The C-terminal transmembrane helix has to undergo a conformational change for potassium ions to access the central cavity. Whereas a partial opening of the tetrameric channel is suggested to be responsible for subconductance levels of ion channels, including KcsA, a cooperative opening of the 4 subunits is postulated as the final opening step. In this study, we used single-channel fluorescence spectroscopy of KcsA to directly observe the movement of each subunit and the temporal correlation between subunits. Purified KcsA channels labeled at the C terminus near the bundle crossing have been inserted into supported lipid bilayer, and the fluorescence traces analyzed by means of a cooperative or independent Markov model. The analysis revealed that the 4 subunits do not move fully independently but instead showed a certain degree of cooperativity. However, the 4 subunits do not simply open in 1 concerted step.
Cloning and characterization of
SARI
(suppressor of AP-1, regulated by IFN)
Authors: Su Zao-zhong , Lee Seok-Geun , Emdad Luni , Lebdeva Irina V. , Gupta Pankaj , Valerie Kristoffer , Sarkar Devanand , Fisher Paul B.
Published: December 2008

We describe a novel basic leucine zipper containing type I IFN-inducible early response gene
SARI
(Suppressor of AP-1, Regulated by IFN). Steady-state
SARI
mRNA expression was detected in multiple lineage-specific normal cells, but not in their transformed/tumorigenic counterparts. In normal and cancer cells,
SARI
expression was induced 2 h after fibroblast IFN (IFN-β) treatment with 1 U/ml of IFN-β. Antisense inhibition of
SARI
protected HeLa cells from IFN-β-mediated growth inhibition. As a corollary, overexpression of SARI inhibited growth and induced apoptosis in cancer cells, but not in normal cells. SARI interacted with c-Jun via its leucine zipper, resulting in inhibition of DNA binding of activator protein (AP-1) complex and consequently AP-1-dependent gene expression. Transformed cells relying on AP-1 activity for proliferative advantage demonstrated increased susceptibility to
SARI
-mediated growth inhibition. These findings uncover a novel mode of IFN-induced anti-tumor growth suppression and suggest potential gene therapy applications for
SARI
.
Mechanism of apoptosis induction by inhibition of the anti-apoptotic BCL-2 proteins
Authors: Chipuk Jerry E. , Fisher John C. , Dillon Christopher P. , Kriwacki Richard W. , Kuwana Tomomi , Green Douglas R.
Published: December 2008

Normal cellular lifespan is contingent upon preserving outer mitochondrial membrane (OMM) integrity, as permeabilization promotes apoptosis. BCL-2 family proteins control mitochondrial outer membrane permeabilization (MOMP) by regulating the activation of the pro-apoptotic BCL-2 effector molecules, BAX and BAK. Sustainable cellular stress induces proteins (e.g., BID, BIM, and cytosolic p53) capable of directly activating BAX and/or BAK, but these direct activators are sequestered by the anti-apoptotic BCL-2 proteins (e.g., BCL-2, BCL-xL, and MCL-1). In the event of accumulated or marked cellular stress, a coordinated effort between previously sequestered and nascent BH3-only proteins inhibits the anti-apoptotic BCL-2 repertoire to promote direct activator protein-mediated MOMP. We examined the effect of ABT-737, a BCL-2 antagonist, and PUMA, a BH3-only protein that inhibits the entire anti-apoptotic BCL-2 repertoire, with cells and mitochondria that sequestered direct activator proteins. ABT-737 and PUMA cooperated with sequestered direct activator proteins to promote MOMP and apoptosis, which in the absence of ABT-737 or PUMA did not influence OMM integrity or cellular survival. Our data show that the induction of apoptosis by inhibition of the anti-apoptotic BCL-2 repertoire requires “covert” levels of direct activators of BAX and BAK at the OMM.
CTCF-dependent enhancer-blocking by alternative chromatin loop formation
Authors: Hou Chunhui , Zhao Hui , Tanimoto Keiji , Dean Ann
Published: December 2008

The mechanism underlying enhancer-blocking by insulators is unclear. We explored the activity of human β-globin HS5, the orthologue of the CTCF-dependent chicken HS4 insulator. An extra copy of HS5 placed between the β-globin locus control region (LCR) and downstream genes on a transgene fulfills the classic predictions for an enhancer-blocker. Ectopic HS5 does not perturb the LCR but blocks gene activation by interfering with RNA pol II, activator and coactivator recruitment, and epigenetic modification at the downstream β-globin gene. Underlying these effects, ectopic HS5 disrupts chromatin loop formation between β-globin and the LCR, and instead forms a new loop with endogenous HS5 that topologically isolates the LCR. Both enhancer-blocking and insulator-loop formation depend on an intact CTCF site in ectopic HS5 and are sensitive to knock-down of the CTCF protein by siRNA. Thus, intrinsic looping activity of CTCF sites can nullify LCR function.
Dissociation of the neuronal regulation of bone mass and energy metabolism by leptin in vivo
Authors: Shi Yu , Yadav Vijay K. , Suda Nina , Liu X. Sherry , Guo X. Edward , Myers Martin G. , Karsenty Gerard
Published: December 2008

The leptin regulation of bone remodeling, which has been documented through studies of loss-of-function mutations of this hormone or of its receptor in mice and humans, still raised several unanswered questions. For instance, it has been assumed but not formally demonstrated that this regulation occurs through neuronal means. Likewise, it has not been possible until now to dissociate the influence leptin exerts on appetite and energy expenditure from this function. We show here through mouse genetic studies that a deletion of the leptin receptor in neurons results in an increase in bone formation and bone resorption, resulting in a high bone mass as seen in leptin-deficient mice. In contrast, the same deletion in osteoblasts only does not influence bone remodeling. Furthermore, through the use of
l
/
l
mice, a model of gain of function in leptin signaling harboring a Y985L substitution in the leptin receptor, we show that leptin signaling inhibits bone mass accrual by up-regulating sympathetic activity independently of any change in appetite or energy expenditure. This work establishes that in vivo leptin regulates bone mass accrual by acting through neuronal means and provides a direct demonstration that this function of leptin can occur independently of its regulation of energy metabolism.
Human Rad52-mediated homology search and annealing occurs by continuous interactions between overlapping nucleoprotein complexes
Authors: Rothenberg Eli , Grimme Jill M. , Spies Maria , Ha Taekjip
Published: December 2008

The Rad52 protein has critical functions in distinct pathways of the homology-directed DNA repair, one of which is to promote the annealing of complementary strands of DNA. Both yeast and human Rad52 proteins organize into ring-shaped oligomers with the predominant form being a heptamer. Despite the wealth of information obtained in previous investigations, how Rad52 mediates homology search and annealing remains unclear. Here, we developed single-molecule fluorescence resonance energy transfer approaches to probe hRad52-mediated DNA annealing events in real time. We found that annealing proceeds in successive steps involving rearrangements of the ssDNA–hRad52 complex. Moreover, after initial pairing, further search for extended homology occurs without dissociation. This search process is driven by an interaction between 2 overlapping nucleoprotein complexes. In light of these observations we propose a model for hRad52-mediated DNA annealing where ssDNA release and dsDNA zippering are coordinated through successive rearrangement of overlapping nucleoprotein complexes.
GRIP1-associated SET-domain methyltransferase in glucocorticoid receptor target gene expression
Authors: Chinenov Yurii , Sacta Maria A. , Cruz Anna R. , Rogatsky Inez
Published: December 2008

Transcriptional regulators such as the glucocorticoid receptor (GR) recruit multiple cofactors to activate or repress transcription. Although most cofactors are intrinsically bifunctional, little is known about the molecular mechanisms dictating the specific polarity of regulation. Furthermore, chromatin modifications thought to be confined to silent loci appear in actively transcribed genes suggesting that similar enzymatic activities may mediate constitutive and transient chromatin states. GRIP1, a GR ligand-dependent coregulator of the p160 family can potentiate or inhibit transcription but the molecular contexts and mechanisms that enable GRIP1 corepressor activity are poorly understood. In a yeast 2-hybrid screen with GRIP1 repression domain (RD)-containing fragment, we repeatedly isolated the C-terminal region of a SET domain-containing protein subsequently identified as histone H4 lysine 20 trimethyltransferase, Suv4-20h1. We cloned a full-length Suv4-20h1 and dissected its interaction with GRIP1 in yeast, in vitro, and in mammalian cells. Strict nuclear localization and high salt concentration required for Suv4-20h1 extraction were consistent with its tight association with chromatin. Overexpression of Suv4-20h1 in human U2OS and A549 cells expressing integrated and endogenous GR, respectively, antagonized ligand-dependent induction of a subset of GR target genes, whereas Suv4-20h1 siRNA-mediated depletion had a reciprocal effect. Inhibition of GR transactivation required both the GRIP1 interacting region of Suv4-20h1 and its catalytic activity. Thus, Suv4-20h1 known exclusively as a factor involved in constitutive heterochromatin maintenance, actively participates in hormone-dependent transcriptional regulation affecting GR target gene expression in a promoter- and cell type-specific manner.
Late Neandertals in Southeastern Iberia: Sima de las Palomas del Cabezo Gordo, Murcia, Spain
Authors: Walker Michael J. , Gibert Josep , López Mariano V. , Lombardi A. Vincent , Pérez-Pérez Alejandro , Zapata Josefina , Ortega Jon , Higham Thomas , Pike Alistair , Schwenninger Jean-Luc , Zilhão João , Trinkaus Erik
Published: December 2008

Middle Paleolithic fossil human remains from the Sima de las Palomas in southeastern Iberia (dated to ≤43,000–40,000 calendar years before present) present a suite of derived Neandertal and/or retained ancestral morphological features in the mandibular symphysis, mandibular ramus, dental occlusal morphology, and distal hand phalanx. These traits are combined with variation in the mandibular corpus, discrete dental morphology, tooth root lengths, and anterior dental size that indicate a frequency difference with earlier Iberian and more northern European Neandertals. The Palomas Neandertals therefore confirm the late presence of Neandertals associated with the Iberian persistence of the Middle Paleolithic, but suggest microevolutionary processes and/or population contact with contemporaneous modern humans to the north.
The structural basis of integrin-linked kinase–PINCH interactions
Authors: Chiswell Brian P. , Zhang Rong , Murphy James W. , Boggon Titus J. , Calderwood David A.
Published: December 2008

The heterotrimeric complex between integrin-linked kinase (ILK), PINCH, and parvin is an essential signaling platform, serving as a convergence point for integrin and growth-factor signaling and regulating cell adhesion, spreading, and migration. We report a 1.6-Å crystal structure of the ILK ankyrin repeat domain bound to the PINCH1 LIM1 domain, revealing the molecular basis of ILK-PINCH interactions and providing a structural description of this region of ILK. This structure identifies 5 ankyrin repeats in ILK, explains previous deletion mutagenesis data, permits identification of ILK and PINCH1 point mutations that disrupt the interaction, shows how zincs are coordinated by PINCH1 LIM1, and suggests that conformational flexibility and twisting between the 2 zinc fingers within the LIM1 domain may be important for ILK binding. These data provide an atomic-resolution description of a key interaction in the ILK–PINCH–parvin scaffolding complex.
From key words to key semantic domains
Authors: Rayson Paul
Published: December 2008

This paper reports the extension of the key words method for the comparison of corpora. Using automatic tagging software that assigns part-of-speech and semantic field (domain) tags, a method is described which permits the extraction of key domains by applying the keyness calculation to tag frequency lists. The combination of the key words and key domains methods is shown to allow macroscopic analysis (the study of the characteristics of whole texts or varieties of language) to inform the microscopic level (focussing on the use of a particular linguistic feature) and thereby suggesting those linguistic features which should be investigated further. The resulting ‘data-driven’ approach presented here combines elements of both the ‘corpus-based’ and ‘corpus-driven’ paradigms in corpus linguistics. A web-based tool, Wmatrix, implementing the proposed method is applied in a case study: the comparison of UK 2001 general election manifestos of the Labour and Liberal Democratic parties.
Quorum responses and consensus decision making
Authors: Sumpter David J.T , Pratt Stephen C
Published: December 2008

Animal groups are said to make consensus decisions when group members come to agree on the same option. Consensus decisions are taxonomically widespread and potentially offer three key benefits: maintenance of group cohesion, enhancement of decision accuracy compared with lone individuals and improvement in decision speed. In the absence of centralized control, arriving at a consensus depends on local interactions in which each individual's likelihood of choosing an option increases with the number of others already committed to that option. The resulting positive feedback can effectively direct most or all group members to the best available choice. In this paper, we examine the functional form of the individual response to others' behaviour that lies at the heart of this process. We review recent theoretical and empirical work on consensus decisions, and we develop a simple mathematical model to show the central importance to speedy and accurate decisions of
quorum responses
, in which an animal's probability of exhibiting a behaviour is a sharply nonlinear function of the number of other individuals already performing this behaviour. We argue that systems relying on such quorum rules can achieve cohesive choice of the best option while also permitting adaptive tuning of the trade-off between decision speed and accuracy.
Leadership, consensus decision making and collective behaviour in humans
Authors: Dyer John R.G , Johansson Anders , Helbing Dirk , Couzin Iain D , Krause Jens
Published: December 2008

This paper reviews the literature on leadership in vertebrate groups, including recent work on human groups, before presenting the results of three new experiments looking at leadership and decision making in small and large human groups. In experiment 1, we find that both group size and the presence of uninformed individuals can affect the speed with which small human groups (eight people) decide between two opposing directional preferences and the likelihood of the group splitting. In experiment 2, we show that the spatial positioning of informed individuals within small human groups (10 people) can affect the speed and accuracy of group motion. We find that having a mixture of leaders positioned in the centre and on the edge of a group increases the speed and accuracy with which the group reaches their target. In experiment 3, we use large human crowds (100 and 200 people) to demonstrate that the trends observed from earlier work using small human groups can be applied to larger crowds. We find that only a small minority of informed individuals is needed to guide a large uninformed group. These studies build upon important theoretical and empirical work on leadership and decision making in animal groups.
Information aggregation and communication in committees
Authors: Austen-Smith David , Feddersen Timothy J
Published: December 2008

In this paper, we attempt to explain the underlying strategic incentives confronting individuals when they must make a collective decision over a set of alternatives and each has information that is decision-relevant for others. A significant literature has emerged in formal political theory over the past several years that focuses on such problems, paying particular attention, first, to the extent to which voting can be expected to aggregate committee members' information and, second, to the role of communication among committee members prior to voting.
Inter alia
, this literature reveals a surprisingly subtle interaction between the voting rules used to make decisions and the incentives for committee members to share information prior to voting.
Group decisions in humans and animals: a survey
Authors: Conradt Larissa , List Christian
Published: December 2008

Humans routinely make many decisions collectively, whether they choose a restaurant with friends, elect political leaders or decide actions to tackle international problems, such as climate change, that affect the future of the whole planet. We might be less aware of it, but group decisions are just as important to social animals as they are for us. Animal groups have to collectively decide about communal movements, activities, nesting sites and enterprises, such as cooperative breeding or hunting, that crucially affect their survival and reproduction. While human group decisions have been studied for millennia, the study of animal group decisions is relatively young, but is now expanding rapidly. It emerges that group decisions in animals pose many similar questions to those in humans. The purpose of the present issue is to integrate and combine approaches in the social and natural sciences in an area in which theoretical challenges and research questions are often similar, and to introduce each discipline to the other's key ideas, findings and successful methods. In order to make such an introduction as effective as possible, here, we briefly review conceptual similarities and differences between the sciences, and provide a guide to the present issue.
Genome-wide detection and analysis of hippocampus core promoters using DeepCAGE
Authors: Valen Eivind , Pascarella Giovanni , Chalk Alistair , Maeda Norihiro , Kojima Miki , Kawazu Chika , Murata Mitsuyoshi , Nishiyori Hiromi , Lazarevic Dejan , Motti Dario , Marstrand Troels Torben , Tang Man-Hung Eric , Zhao Xiaobei , Krogh Anders , Winther Ole , Arakawa Takahiro , Kawai Jun , Wells Christine , Daub Carsten , Harbers Matthias , Hayashizaki Yoshihide , Gustincich Stefano , Sandelin Albin , Carninci Piero
Published: December 2008

Finding and characterizing mRNAs, their transcription start sites (TSS), and their associated promoters is a major focus in post-genome biology. Mammalian cells have at least 5–10 magnitudes more TSS than previously believed, and deeper sequencing is necessary to detect all active promoters in a given tissue. Here, we present a new method for high-throughput sequencing of 5′ cDNA tags—DeepCAGE: merging the Cap Analysis of Gene Expression method with ultra-high-throughput sequence technology. We apply DeepCAGE to characterize 1.4 million sequenced TSS from mouse hippocampus and reveal a wealth of novel core promoters that are preferentially used in hippocampus: This is the most comprehensive promoter data set for any tissue to date. Using these data, we present evidence indicating a key role for theArnt2transcription factor in hippocampus gene regulation. DeepCAGE can also detect promoters used only in a small subset of cells within the complex tissue.
Autophagy Plays a Role in Chloroplast Degradation during Senescence in Individually Darkened Leaves
Authors: Wada Shinya , Ishida Hiroyuki , Izumi Masanori , Yoshimoto Kohki , Ohsumi Yoshinori , Mae Tadahiko , Makino Amane
Published: December 2008

Chloroplasts contain approximately 80% of total leaf nitrogen and represent a major source of recycled nitrogen during leaf senescence. While bulk degradation of the cytosol and organelles in plants is mediated by autophagy, its role in chloroplast catabolism is largely unknown. We investigated the effects of autophagy disruption on the number and size of chloroplasts during senescence. When leaves were individually darkened, senescence was promoted similarly in both wild-type Arabidopsis (Arabidopsis thaliana) and in an autophagy-defective mutant, atg4a4b-1. The number and size of chloroplasts decreased in darkened leaves of wild type, while the number remained constant and the size decrease was suppressed in atg4a4b-1. When leaves of transgenic plants expressing stroma-targeted DsRed were individually darkened, a large accumulation of fluorescence in the vacuolar lumen was observed. Chloroplasts exhibiting chlorophyll fluorescence, as well as Rubisco-containing bodies, were also observed in the vacuole. No accumulation of stroma-targeted DsRed, chloroplasts, or Rubisco-containing bodies was observed in the vacuoles of the autophagy-defective mutant. We have succeeded in demonstrating chloroplast autophagy in living cells and provide direct evidence of chloroplast transportation into the vacuole.
Chronic intermittentL‐DOPA treatment induces changes in dopamine release
Authors: Lundblad Martin , Af Bjerkén Sara , Cenci M. Angela , Pomerleau Francois , Gerhardt Greg A. , Strömberg Ingrid
Published: December 2008

3,4‐Dihydroxyphenyl‐l‐alanine(l‐DOPA)‐induced dyskinesia often develops as a side effect of chronicl‐DOPA therapy. This study was undertaken to investigate dopamine (DA) release uponl‐DOPA treatment. Chronoamperometric measurements were performed in unilaterally DA‐depleted rats, chronically treated withl‐DOPA, resulting in dyskinetic and non‐dyskinetic animals. Normal and lesionedl‐DOPA naïve animals were used as controls. Potassium‐evoked DA releases were significantly reduced in intact sides of animals undertaken chronicl‐DOPA treatment, independent on dyskinetic behavior. Acutel‐DOPA further attenuated the amplitude of the DA release in the control sides. In DA‐depleted striata, no difference was found in potassium‐evoked DA releases, and acutel‐DOPA did not affect the amplitude. While immunoreactivity to serotonin uptake transporter was higher in lesioned striata of animals displaying dyskinetic behavior, no correlation could be documented between serotonin transporter‐positive nerve fiber density and the amplitude of released DA. In conclusions, the amplitude of potassium‐evoked DA release is attenuated in intact striatum after chronic intermittentl‐DOPA treatment. No change in amplitude was found in DA‐denervated sides of either dyskinetic or non‐dyskinetic animals, while release kinetics were changed. This indicates the importance of studying DA release dynamics for the understanding of both beneficial and adverse effects ofl‐DOPA replacement therapy.
RNA editing of the serotonin 2C receptor and expression of Gαqprotein: genetic mouse models do not support a role for regulation or compensation
Authors: Canal Clinton E. , Mahautmr Kontip C. , Cao Chike , Sanders‐Bush Elaine , Airey David C.
Published: December 2008

The serotonin 2C (5‐HT2C) receptor undergoes RNA editing at five bases in a region of the pre‐mRNA encoding the second intracellular loop, generating many unique 5‐HT2Creceptor isoforms. Mechanisms regulatingin vivoexpression of different edited 5‐HT2Creceptor isoforms are poorly understood, as are the adaptive consequences of variation in editing profiles. Recent findings suggest a putative relationship between expression levels of Gαq/11protein and the degree of editing of 5‐HT2Creceptor transcripts. To elucidate the potential regulatory or adaptive role of Gαq/11protein levels, we quantified editing of 5‐HT2Creceptor RNA transcripts in Gαqnull mice and protein levels of Gαqand Gα11in transgenic male mice solely expressing either the non‐edited (INI) or the fully edited (VGV) isoforms of the 5‐HT2Creceptor. Pyrosequencing of RNA isolated from amygdaloid cortex in Gαqnull and wild‐type mice revealed no significant differences in 5‐HT2Creceptor mRNA editing profiles. Cortical tissue from INI/y, VGV/y, and wild‐type mice was assayed for expression of Gαqand Gα11subunits by Western blotting. No differences in signal density between wild‐type and INI/y or VGV/y groups were found, indicating equivalent levels of Gαqand Gα11protein. Together, these data do not support a causal or compensatory relationship between 5‐HT2Creceptor RNA editing and Gqprotein levels.
Cell volume control in phospholemman (PLM) knockout mice: do cardiac myocytes demonstrate a regulatory volume decrease and is this influenced by deletion of PLM?
Authors: Bell James R. , Lloyd David , Curl Claire L. , Delbridge Lea M. D. , Shattock Michael J.
Published: December 2008

In addition to modulatory actions on Na+–K+‐ATPase, phospholemman (PLM) has been proposed to play a role in cell volume regulation. Overexpression of PLM induces ionic conductances, with ‘PLM channels’ exhibiting selectivity for taurine. Osmotic challenge of host cells overexpressing PLM increases taurine efflux and augments the cellular regulatory volume decrease (RVD) response, though a link between PLM and cell volume regulation has not been studied in the heart. We recently reported a depressed cardiac contractile function in PLM knockout mice in vivo, which was exacerbated in crystalloid‐perfused isolated hearts, indicating that these hearts were osmotically challenged. To address this, the present study investigated the role of PLM in osmoregulation in the heart. Isolated PLM wild‐type and knockout hearts were perfused with a crystalloid buffer supplemented with mannitol in a bid to prevent perfusate‐induced cell swelling and maintain function. Accordingly, and in contrast to wild‐type control hearts, contractile function was improved in PLM knockout hearts with 30 mm mannitol. To investigate further, isolated PLM wild‐type and knockout cardiomyocytes were subjected to increasing hyposmotic challenges. Initial validation studies showed the IonOptix video edge‐detection system to be a simple and accurate ‘real‐time’ method for tracking cell width as a marker of cell size. Myocytes swelled equally in both genotypes, indicating that PLM, when expressed at physiological levels in cardiomyocytes, is not essential to limit water accumulation in response to a hyposmotic challenge. Interestingly, freshly isolated adult cardiomyocytes consistently failed to mount RVDs in response to cell swelling, adding to conflicting reports in the literature. A proposed perturbation of the RVD response as a result of the cell isolation process was not restored, however, with short‐term culture in either adult or neonatal cardiomyocytes.