An attractor network is a network of neurons with excitatory interconnections that can settle into a stable pattern of firing. This article shows how attractor networks in the cerebral cortex are important for long-term memory, short-term memory, attention, and decision making. The article then shows how the random firing of neurons can influence the stability of these networks by introducing stochastic noise, and how these effects are involved in probabilistic decision making, and implicated in some disorders of cortical function such as poor short-term memory and attention, schizophrenia, and obsessive-compulsive disorder. Copyright © 2009 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website.

Adult skeletal muscle possesses remarkable regenerative capacity that has conventionally been attributed to the satellite cells. These precursor cells were thought to contain distinct populations with varying myogenic potential. Recently, the identification of multipotent stem cells capable of new myofiber formation has expanded the general view on the muscle regenerative process. Here we examined the characteristics of turkey skeletal muscle-derived cell (MDC) populations that were separated according to their adhesion abilities. We sought to determine whether these abilities could be a potential tool for separating cells with different myogenic commitment. Using the preplate technique, we showed that MDCs display a wide range of adhesion ability, allowing us to isolate a marginal fraction with initial adhesion defect. Methodological investigations revealed that this defect represents an intrinsic and well-established biological feature for these cells. In vitro behavioral and morphological analyses showed that late adherent cells (LACs) share several primitive cell characteristics. Phenotypic assessment indicated that LACs contain early stage myogenic cells and immature progenitors of satellite cells, whereas early adherent cells consist mainly of fully committed precursors. Overall, our findings demonstrate for the first time in an avian model that differential MDC adhesion properties could be used to efficiently purify cells with varying myogenic commitment, including immature progenitor cells. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

The sleeping sickness trypanosomes Trypanosoma brucei rhodesiense and T. brucei gambiense are morphologically indistinguishable from each other and from T. brucei brucei, which does not infect humans. The relationships between these three subspecies have been controversial. Several years ago, the characterization of T. brucei gambiense was reviewed in an attempt to clarify and draw together the results, and to put them in the context of the biology of the organism. The discovery of a gene associated with human-serum resistance in T. brucei rhodesiense and the consequent reappraisal of the identity of this trypanosome prompt this companion article.

Vaginal practices are a variety of behavioral techniques that women use to manage their sexual life and personal hygiene. Women perceive vaginal practices as a beneficial practice. However, vaginal cleansing has been identified as one of the main risk factors for bacterial vaginosis and is potentially implicated in Human Immune Deficiency Virus (HIV) and sexually transmitted infection transmission. This study examined the prevalence of vaginal practices and the types of practices used among a sample of HIV positive women living in Lusaka, Zambia. Over 90% of all women recruited engaged in vaginal practices. Certain practices, such as use of water or soap, were more frequently used for hygiene reasons. Herbs and traditional medicines were mainly used to please sexual partner. Strategies to decrease VP appear urgently needed in the Zambian community.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Image duplication has been observed within Figure 1g-h. The corresponding author has been asked to provide an acceptable explanation for this duplication but has not been able to do so neither have the original source files been supplied.

This discussion of forehead lifting, based on modifications of Vinas, Caviglia, and Cortinas, shares the authors' methods of patient evaluation, diagnostic details, architectural planning, and surgical concepts for forehead rhytidectomy along with correction of malpositioned and ptosis of the eyebrows and also glabellar frown problems. In addition, the nasal deformities associated with the sagging of the skin and subcutaneous tissue onto the upper fourth of the nose may make the nose look too short for a pleasing balance of the face and the upper fourth may appear disagreeably wide. A contribution to this excessive width is made by a sometimes thick and wide procerus muscle along with bilateral thick depressor supercilii muscles. When this nasal deformity is corrected, glabellar frown problems are also corrected. Attention to the details of the above-mentioned factors results in very long-lasting, sometimes permanent, and almost complication-free results that please the surgeon and the patient. Complications such as adherence of the dermis to the underlying pericranium, lack of motion in a portion of or the entire forehead, hyperactivity around areas of immobility, muscle irregularities, and also surgically produced depressions which require grafting, skin sloughing, permanent nerve injury, persistent sensory nerve loss, and short-term improvement have been avoided by paying attention to diagnosis, surgical planning, and technique, and postoperative care. Most patients can return to work in four or five days with minimal discoloration and swelling if they have not had aspirin or vitamin E one month before surgery, and there is hemostasis and the use of drains when indicated. Minimizing detection of the surgical incisions is accomplished by detailed preoperative planning of their location, architectural design development and drawing at the time of surgery, special surgical techniques, and excision of the skin or scalp. For patients with male pattern baldness use of specially designed V-Y advancement flaps with the browlift procedure improve the appearance of the hair's thickness and distribution.

Cat-scratch disease has been recognized since 1889 in association with the oculoglandular syndrome of Parinaud. The epidemiologic association with cats was first made in 1931 and further substantiated throughout the years, refining the interaction predominantly to kittens. Putative infectious agents have included numerous species of bacteria, chlamydiae, and viruses. The cultivation of Afipia spp. in the late 1980s appeared to answer the mystery of the identity of the agent. However, even more recent analysis, which has combined traditional microbiology, molecular methods, and additional epidemiology, has demonstrated that Bartonella (Rochalimaea) henselae is the definitive agent of cat-scratch disease. Our understanding of the pathogenesis of cat-scratch disease and other diseases caused by Bartonella species is incomplete and the spectrum of diseases continues to emerge. We review historic and modern efforts to understand the etiology of cat-scratch disease and related syndromes.

BACKGROUND

There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2-5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2-5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4 percentage (CD4%) <25%.

RESULTS

ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm(3) (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1-6.5) (no ART) to 2.1% (95% CI: 1.3%-3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%-3.5%) and 2.2% (95% CI: 1.4%-3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data.

CONCLUSIONS

The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm(3) or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors' Summary.

Functionalist typologists have long argued that pressures associated with language usage influence the distribution of grammatical properties across the world's languages. Specifically, grammatical properties may be observed more often across languages because they improve a language's utility or decrease its complexity. While this approach to the study of typology offers the potential of explaining grammatical patterns in terms of general principles rather than domain-specific constraints, the notions of utility and complexity are more often grounded in intuition than empirical findings. A suitable empirical foundation might be found in the terms of processing preferences: in that case, psycholinguistic measures of complexity are then expected correlate with typological patterns. We summarize half a century of psycholinguistic work on 'processing complexity' in an attempt to make this work accessible to a broader audience: What makes something hard to process for comprehenders, and what determines speakers' preferences in production? We also briefly discuss recently emerging approaches that link preferences in production to communicative efficiency. These approaches can be seen as providing well-defined measures of utility. With these psycholinguistic findings in mind, it is possible to investigate the extent to which language usage is reflected in typological patterns. We close with a summary of paradigms that allow the link between language usage and typology to be studied empirically. WIREs Cogni Sci 2011 2 323-335 DOI: 10.1002/wcs.126 For further resources related to this article, please visit the WIREs website.

Analysis of spontaneously correlated low-frequency activity fluctuations across the brain using functional magnetic resonance imaging (MRI)-commonly referred to as resting-state functional connectivity (RSFC) MRI-was initially seen as a useful tool for mapping functional-anatomic networks in the living human brain, characterizing brain changes and differences in clinical populations, and studying comparative anatomy across species. However, little was known about the potential relevance of RSFC to cognitive processes. Indeed, there has been considerable controversy and debate as to the utility of studying the resting-state in cognitive neuroscience. However, recent work has shown that RSFC, rather than merely reflecting passive or epiphenomenal activity within underlying functional-anatomic networks, reveals important dynamic processes that play an active role in cognition. RSFC has been associated with individual differences in a number of behavioral and cognitive domains, including perception, language, learning and memory, and the organization of conceptual knowledge. In this article, we review and integrate the latest research demonstrating that RSFC is functionally relevant to human behavior and higher-level cognition, and propose a hypothesis regarding its mechanism of action on functional network dynamics and cognition. We conclude that RSFC MRI will be an invaluable tool for future discovery of the fundamental neurocognitive interactions that underlie cognition. WIREs Cogn Sci 2014, 5:233-245. doi: 10.1002/wcs.1275 CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website.

BACKGROUND

Oxytocin (10 IU) is the drug of choice for prevention of postpartum hemorrhage (PPH). Its use has generally been restricted to medically trained staff in health facilities. We assessed the effectiveness, safety, and feasibility of PPH prevention using oxytocin injected by peripheral health care providers without midwifery skills at home births.

RESULTS

This community-based, cluster-randomized trial was conducted in four rural districts in Ghana. We randomly allocated 54 community health officers (stratified on district and catchment area distance to a health facility: ≥10 km versus <10 km) to intervention (one injection of oxytocin [10 IU] one minute after birth) and control (no provision of prophylactic oxytocin) arms. Births attended by a community health officer constituted a cluster. Our primary outcome was PPH, using multiple definitions; (PPH-1) blood loss ≥500 mL; (PPH-2) PPH-1 plus women who received early treatment for PPH; and (PPH-3) PPH-2 plus any other women referred to hospital for postpartum bleeding. Unsafe practice is defined as oxytocin use before delivery of the baby. We enrolled 689 and 897 women, respectively, into oxytocin and control arms of the trial from April 2011 to November 2012. In oxytocin and control arms, respectively, PPH-1 rates were 2.6% versus 5.5% (RR: 0.49; 95% CI: 0.27-0.88); PPH-2 rates were 3.8% versus 10.8% (RR: 0.35; 95% CI: 0.18-0.63), and PPH-3 rates were similar to those of PPH-2. Compared to women in control clusters, those in the intervention clusters lost 45.1 mL (17.7-72.6) less blood. There were no cases of oxytocin use before delivery of the baby and no major adverse events requiring notification of the institutional review boards. Limitations include an unblinded trial and imbalanced numbers of participants, favoring controls.

CONCLUSIONS

Maternal health care planners can consider adapting this model to extend the use of oxytocin into peripheral settings including, in some contexts, home births.

BACKGROUND

ClinicalTrials.gov NCT01108289 Please see later in the article for the Editors' Summary.

BACKGROUND

The development of an integrated genetic and physical map for the maize genome involves the generation of an enormous amount of data. Managing this data requires a system to aid in genotype scoring for different types of markers coming from both local and remote users. In addition, researchers need an efficient way to interact with genetic mapping software and with data files from automated DNA sequencing. They also need ways to manage primer data for mapping and sequencing and provide views of the integrated physical and genetic map and views of genetic map comparisons.

RESULTS

The MMP-LIMS system has been used successfully in a high-throughput mapping environment. The genotypes from 957 SSR, 1023 RFLP, 189 SNP, and 177 InDel markers have been entered and verified via MMP-LIMS. The system is flexible, and can be easily modified to manage data for other species. The software is freely available.

BACKGROUND

To receive a copy of the iMap or cMap software, please fill out the form on our website. The other MMP-LIMS software is freely available at http://www.maizemap.org/bioinformatics.htm.

The neuronal apoptosis inhibitory protein (NAIP) gene, also known as the baculovirus inhibitor of apoptosis repeat-containing protein 1 (BIRC1) gene, is a member of the inhibitors of apoptosis (IAP) family and was first characterized as a candidate gene for spinal muscular atrophy (SMA). The expression of NAIP has been thoroughly studied in the central nervous system and overlaps the pattern of neurodegeneration in SMA. Recent studies have pointed to a role for NAIP in non-neuronal cells. We report here the production of a specific anti-NAIP antibody and the profile of NAIP expression in human adult tissues by Western blot and immunohistochemical detection methods. NAIP was detected in a number of tissues by Western blot analysis, but immunohistochemistry revealed that NAIP's presence in certain tissues, such as liver, lung, and spleen, is most likely due to macrophage infiltration. In the small intestine, the expression of NAIP coincides with the expression of p21(WAF1). This observation, coupled with findings from other groups, suggests a role for NAIP in increasing the survival of cells undergoing terminal differentiation as well as the possibility that the protein serves as an intestinal pathogen recognition protein. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

Human embryonic stem cells (HESCs) carrying specific mutations potentially provide a valuable tool for studying genetic disorders in humans. One preferable approach for obtaining these cell lines is by deriving them from affected preimplantation genetically diagnosed embryos. These unique cells are especially important for modeling human genetic disorders for which there are no adequate research models. They can be further used to gain new insights into developmentally regulated events that occur during human embryo development and that are responsible for the manifestation of genetically inherited disorders. They also have great value for the exploration of new therapeutic protocols, including gene-therapy-based treatments and disease-oriented drug screening and discovery. Here, we report the establishment of 15 different mutant human embryonic stem cell lines derived from genetically affected embryos, all donated by couples undergoing preimplantation genetic diagnosis in our in vitro fertilization unit. For further information regarding access to HESC lines from our repository, for research purposes, please email dalitb@tasmc.health.gov.il.

BACKGROUND

Artemisinin combination therapies (ACTs) with broad efficacy are needed where multiple Plasmodium species are transmitted, especially in children, who bear the brunt of infection in endemic areas. In Papua New Guinea (PNG), artemether-lumefantrine is the first-line treatment for uncomplicated malaria, but it has limited efficacy against P. vivax. Artemisinin-naphthoquine should have greater activity in vivax malaria because the elimination of naphthoquine is slower than that of lumefantrine. In this study, the efficacy, tolerability, and safety of these ACTs were assessed in PNG children aged 0.5-5 y.

RESULTS

An open-label, randomized, parallel-group trial of artemether-lumefantrine (six doses over 3 d) and artemisinin-naphthoquine (three daily doses) was conducted between 28 March 2011 and 22 April 2013. Parasitologic outcomes were assessed without knowledge of treatment allocation. Primary endpoints were the 42-d P. falciparum PCR-corrected adequate clinical and parasitologic response (ACPR) and the P. vivax PCR-uncorrected 42-d ACPR. Non-inferiority and superiority designs were used for falciparum and vivax malaria, respectively. Because the artemisinin-naphthoquine regimen involved three doses rather than the manufacturer-specified single dose, the first 188 children underwent detailed safety monitoring. Of 2,542 febrile children screened, 267 were randomized, and 186 with falciparum and 47 with vivax malaria completed the 42-d follow-up. Both ACTs were safe and well tolerated. P. falciparum ACPRs were 97.8% and 100.0% in artemether-lumefantrine and artemisinin-naphthoquine-treated patients, respectively (difference 2.2% [95% CI -3.0% to 8.4%] versus -5.0% non-inferiority margin, p = 0.24), and P. vivax ACPRs were 30.0% and 100.0%, respectively (difference 70.0% [95% CI 40.9%-87.2%], p<0.001). Limitations included the exclusion of 11% of randomized patients with sub-threshold parasitemias on confirmatory microscopy and direct observation of only morning artemether-lumefantrine dosing.

CONCLUSIONS

Artemisinin-naphthoquine is non-inferior to artemether-lumefantrine in PNG children with falciparum malaria but has greater efficacy against vivax malaria, findings with implications in similar geo-epidemiologic settings within and beyond Oceania.

BACKGROUND

Australian New Zealand Clinical Trials Registry ACTRN12610000913077. Please see later in the article for the Editors' Summary.

The ability to determine an infant's likelihood of developing autism via a relatively simple neurological measure would constitute an important scientific breakthrough. In their recent publication in this journal, Bosl and colleagues claim that a measure of EEG complexity can be used to detect, with very high accuracy, infants at high risk for autism (HRA). On the surface, this appears to be that very scientific breakthrough and as such the paper has received widespread media attention. But a close look at how these high accuracy rates were derived tells a very different story. This stems from a conflation between "high risk" as a population-level property and "high risk" as a property of an individual. We describe the approach of Bosl et al. and examine their results with respect to baseline prevalence rates, the inclusion of which is necessary to distinguish infants with a biological risk of autism from typically developing infants with a sibling with autism. This is an important distinction that should not be overlooked. Please see research article: http://www.biomedcentral.com/1741-7015/9/18 and correspondence article: http://www.biomedcentral.com/1741-7015/9/60.

PR-1 has been extensively used as a marker for salicylic acid (SA)-mediated defence and systemic and local acquired resistance. The Arabidopsis Genome Project annotates At2g19990 as PR-1. This gene is also identified as PR-1 in two "full genome" Arabidopsis microarrays, and TAIR cites approximately 60 articles to describe its patterns of expression. However, most of these citations are incorrect; the probes used were not At2g19990, but a homologous gene At2g14610, which is annotated as "PR-1-like". Because of the potential for confusion, we analyzed the expression of both genes in Arabidopsis thaliana (L.) Heynh. At2g14610 (PR-1-like) showed the archetypal patterns of SA-responsive expression: mRNA levels increased following SA-treatment, inoculation with an avirulent (but not a virulent) strain of Pseudomonas syringae, and in wild-type (but not NahG) Arabidopsis infected with cauliflower mosaic virus (CaMV). In cpr5 mutants it was expressed constitutively. In contrast, expression of At2g19990 (annotated as PR-1) was detectable in neither SA-treated Col-0 nor in cpr5. Infection by virulent and avirulent isolates of P. syringae up-regulated expression, but to a similar level, and infection by CaMV induced a modest increase in expression in both the wild type and NahG. At2g19990, although pathogen responsive, does not show the SA-dependent patterns of expression expected from a member of the PR-1 regulon, and its annotation as " PR-1" is inappropriate. The annotations should identify At2g14610 as the authentic PR-1.

Language and music are the most impressive examples of humans' capacity to process complex sound and structure. Though interest in the relationship between these two abilities has a long history, only recently has cognitive and neuroscientific research started to illuminate both what is shared and what is distinct between linguistic and musical processing. This review considers evidence for a link between language and music at three levels of analysis: sound, structure, and meaning. These links not only inform our understanding of language and music, but also add to a more basic understanding of our processing of complex auditory stimuli, structure, meaning, and emotion. WIREs Cogn Sci 2012, 3:483-492. doi: 10.1002/wcs.1186 For further resources related to this article, please visit the WIREs website.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This retraction was suggested by the University of Cologne Investigation committee and seconded by the authors who the journal was able to contact (Wenz, T., Dillon, L., Diaz, F., Hida, A., and Moraes, C.T.). Following an investigation of the last author, Dr. Tina Wenz, by the University of Cologne, Germany, the university determined that data presented in this article have been inappropriately manipulated https://www.portal.uni-koeln.de/9015.html?&tx_news_pi1%5Bnews%5D=4335&tx_news_pi1%5Bcontroller%5D=News&tx_news_pi1%5Baction%5D=detail&cHash=1deb8399d7f796d65ca9f6ae4764a1ce. Specifically, western blot images in Figure 5F (tubulin in cortex), 2F (COXI in hippocampus) and 3B (Sod2 in hippocampus) were re-used from an earlier article published elsewhere [Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging" Wenz T, Rossi SG, Rotundo RL, Spiegelman BM, and Moraes CT. Proc Natl Acad Sci U S A. 2009;106:20405-10, doi: 10.1073/pnas.0911570106] representing different experimental findings. Therefore, whether or not the main conclusions are still valid, the authors request retraction of this publication because the scientific integrity of the study was compromised. The authors sincerely apologize to the scientific community.

BACKGROUND

UDP-GlcNAc 2-epimerase/ManNAc 6-kinase, GNE, is a bi-functional enzyme that plays a key role in sialic acid biosynthesis. Mutations of the GNE protein cause sialurea or autosomal recessive inclusion body myopathy/Nonaka myopathy. GNE is the only human protein that contains a kinase domain belonging to the ROK (repressor, ORF, kinase) family.

RESULTS

We solved the structure of the GNE kinase domain in the ligand-free state. The protein exists predominantly as a dimer in solution, with small populations of monomer and higher-order oligomer in equilibrium with the dimer. Crystal packing analysis reveals the existence of a crystallographic hexamer, and that the kinase domain dimerizes through the C-lobe subdomain. Mapping of disease-related missense mutations onto the kinase domain structure revealed that the mutation sites could be classified into four different groups based on the location - dimer interface, interlobar helices, protein surface, or within other secondary structural elements.

CONCLUSIONS

The crystal structure of the kinase domain of GNE provides a structural basis for understanding disease-causing mutations and a model of hexameric wild type full length enzyme.

BACKGROUND

This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.

The use of Ritalin and other stimulant drug treatments for attention-deficit hyperactivity disorder (ADHD) raises distinctive moral dilemmas for parents; these moral dilemmas have not been adequately addressed in the bioethics literature. This paper draws upon data from a qualitative empirical study to investigate parents' use of the moral ideal of authenticity as part of their narrative justifications for dosing decisions and actions. I show that therapeutic decisions and actions are embedded in valued cultural ideals about masculinity, self-actualization and success, as well as in moral conceptions of authenticity and personal freedom. I argue that this investigation of parents' moral justifications and dosing dilemmas raises questions about the validity of authenticity as a transcendent moral principle. Moreover, this study demonstrates that in order to be relevant, bioethical analysis of neurocognitive enhancement must engage with ground-up studies of moral principles and decision-making in context.

Casein kinase 1 epsilon (CK1epsilon) is involved in various cellular processes, including cell growth, differentiation, and apoptosis, vesicle transport, and control of the circadian rhythm. Deregulation of CK1epsilon has been linked to neurodegenerative diseases and cancer. To better understand the cell type-specific functions of CK1epsilon, we determined its localization by immunhistochemistry in tissues of healthy, young adult BALB/c mice and in mammary tumors of SV40 T-antigen-transgenic mice. CK1epsilon expression was found to be highly regulated in normal tissues of endodermal, mesodermal, and ectodermal origin and in neoplastic tissue of mammary cancer. The data presented here give an overview of CK1epsilon reactivity in different organs under normal conditions and outline changes in its expression in mammary carcinomas. Our data suggest a cell/organ type-specific function of CK1epsilon and indicate that tumorigenic conversion of mammary glands in SV40 T-antigen-transgenic mice leads to downregulation of CK1epsilon. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.