In a broad variety of bilaterian species the trunk central nervous system (CNS) derives from three primary rows of neuroblasts. The fates of these neural progenitor cells are determined in part by ...three conserved transcription factors: vnd/nkx2.2, ind/gsh and msh/msx in Drosophila melanogaster/vertebrates, which are expressed in corresponding non-overlapping patterns along the dorsal-ventral axis. While this conserved suite of "neural identity" gene expression strongly suggests a common ancestral origin for the patterning systems, it is unclear whether the original regulatory mechanisms establishing these patterns have been similarly conserved during evolution. In Drosophila, genetic evidence suggests that Bone Morphogenetic Proteins (BMPs) act in a dosage-dependent fashion to repress expression of neural identity genes. BMPs also play a dose-dependent role in patterning the dorsal and lateral regions of the vertebrate CNS, however, the mechanism by which they achieve such patterning has not yet been clearly established. In this report, we examine the mechanisms by which BMPs act on cis-regulatory modules (CRMs) that control localized expression of the Drosophila msh and zebrafish (Danio rerio) msxB in the dorsal central nervous system (CNS). Our analysis suggests that BMPs act differently in these organisms to regulate similar patterns of gene expression in the neuroectoderm: repressing msh expression in Drosophila, while activating msxB expression in the zebrafish. These findings suggest that the mechanisms by which the BMP gradient patterns the dorsal neuroectoderm have reversed since the divergence of these two ancient lineages.
Prolactin (PRL) is a pleiotropic hormone that was identified in the context of maternal care and its release from the anterior pituitary is primarily controlled by neuroendocrine dopaminergic (NEDA) ...neurones of the arcuate nucleus of the hypothalamus. The sexually dimorphic nature of PRL physiology and associated behaviours is evident in mammals, even though the number and density of NEDA neurones is reported as not being sexually dimorphic in rats. However, the underlying circuits controlling NEDA neuronal activity and subsequent PRL release are largely uncharacterised. Thus, we mapped whole‐brain monosynaptic NEDA inputs in male and female mice. Accordingly, we employed a rabies virus based monosynaptic tracing system capable of retrogradely mapping inputs into genetically defined neuronal populations. To gain genetic access to NEDA neurones, we used the dopamine transporter promoter. Here, we unravel 59 brain regions that synapse onto NEDA neurones and reveal that male and female mice, despite monomorphic distribution of NEDA neurones in the arcuate nucleus of the hypothalamus, receive sexually dimorphic amount of inputs from the anterior hypothalamic nucleus, anteroventral periventricular nucleus, medial preoptic nucleus, paraventricular hypothalamic nucleus, posterior periventricular nucleus, supraoptic nucleus, suprachiasmatic nucleus, lateral supramammillary nucleus, tuberal nucleus and periaqueductal grey. Beyond highlighting the importance of considering sex as a biological variable when evaluating connectivity in the brain, these results illustrate a case where a neuronal population with similar anatomical distribution has a subjacent sexually dimorphic connectivity pattern, potentially capable of contributing to the sexually dimorphic nature of PRL release and function.
Supplemental Digital Content is Available in the Text.
Light chain amyloidosis (AL) is a complex disorder defined by the extracellular deposition of insoluble amyloid fibrils formed by intact or ...fragmented immunoglobulin light chains, leading to cell dysfunction, rapid organ deterioration, and, ultimately, death. Although the clinical presentation of AL is directly connected to organ involvement, signs and symptoms of AL are frequently nonspecific, misinterpreted, and late recognized. Thus, an early diagnosis combined with effective therapies to cease disease progression and rescue organ function is essential. The aim of this study was to assess the knowledge and characterize the current clinical practice regarding AL diagnosis and referral among Portuguese physicians. A Delphi-like panel (one round only) with a group of national experts from different medical specialties (cardiology, hematology, internal medicine, nephrology, and neurology) was carried out online, in which 30 statements were classified using a 4-point Likert scale. For each statement, the consensus level was set at 70% for “fully agree/disagree” and the majority level was defined as >70% in agreement or disagreement. Although the results suggest the existence of adequate general knowledge of AL amyloidosis, they also disclosed the necessity to raise awareness for this disease. Overall, this Delphi panel revealed a high lack of consensus regarding the diagnosis and early management of patients with AL among different specialties despite the qualified majority obtained in 26 statements. An optimized strategy for AL early diagnosis, transversal to several medical fields, is urgently needed. Moreover, referral centers with access to diagnostic technology and a network of diverse specialties should be established to foster an early diagnosis and better disease approach to boost the possibility of a better outcome for patients with AL.
Booly: a new data integration platform Do, Long H; Esteves, Francisco F; Karten, Harvey J ...
BMC bioinformatics,
10/2010, Letnik:
11, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Data integration is an escalating problem in bioinformatics. We have developed a web tool and warehousing system, Booly, that features a simple yet flexible data model coupled with the ability to ...perform powerful comparative analysis, including the use of Boolean logic to merge datasets together, and an integrated aliasing system to decipher differing names of the same gene or protein. Furthermore, Booly features a collaborative sharing system and a public repository so that users can retrieve new datasets while contributors can easily disseminate new content.
We illustrate the uses of Booly with several examples including: the versatile creation of homebrew datasets, the integration of heterogeneous data to identify genes useful for comparing avian and mammalian brain architecture, and generation of a list of Food and Drug Administration (FDA) approved drugs with possible alternative disease targets.
The Booly paradigm for data storage and analysis should facilitate integration between disparate biological and medical fields and result in novel discoveries that can then be validated experimentally. Booly can be accessed at http://booly.ucsd.edu.
In a broad variety of bilaterian species the trunk central nervous system (CNS) derives from three primary rows of neuroblasts. The fates of these neural progenitor cells are determined in part by ...three conserved transcription factors: vnd/nkx2.2, ind/gsh and msh/msx in Drosophila melanogaster/vertebrates, which are expressed in corresponding non-overlapping patterns along the dorsal-ventral axis. While this conserved suite of "neural identity" gene expression strongly suggests a common ancestral origin for the patterning systems, it is unclear whether the original regulatory mechanisms establishing these patterns have been similarly conserved during evolution. In Drosophila, genetic evidence suggests that Bone Morphogenetic Proteins (BMPs) act in a dosage-dependent fashion to repress expression of neural identity genes. BMPs also play a dose-dependent role in patterning the dorsal and lateral regions of the vertebrate CNS, however, the mechanism by which they achieve such patterning has not yet been clearly established. In this report, we examine the mechanisms by which BMPs act on cis-regulatory modules (CRMs) that control localized expression of the Drosophila msh and zebrafish (Danio rerio) msxB in the dorsal central nervous system (CNS). Our analysis suggests that BMPs act differently in these organisms to regulate similar patterns of gene expression in the neuroectoderm: repressing msh expression in Drosophila, while activating msxB expression in the zebrafish. These findings suggest that the mechanisms by which the BMP gradient patterns the dorsal neuroectoderm have reversed since the divergence of these two ancient lineages.
After much debate, there is an emerging consensus that the composition of many ecological communities is determined both by species traits, as proposed by niche theory, as well as by chance events. A ...critical question for ecology is, therefore, which attributes of species predict the dominance of deterministic or stochastic processes. We outline two hypotheses by which organism size could determine which processes structure ecological communities, and we test these hypotheses by comparing the community structure in bromeliad phytotelmata of three groups of organisms (bacteria, zooplankton, and macroinvertebrates) that encompass a 10 000-fold gradient in body size, but live in the same habitat. Bacteria had no habitat associations, as would be expected from trait-neutral stochastic processes, but still showed exclusion among species pairs, as would be expected from niche-based processes. Macroinvertebrates had strong habitat and species associations, indicating niche-based processes. Zooplankton, with body size between bacteria and macroinvertebrates, showed intermediate habitat associations. We concluded that a key niche process, habitat filtering, strengthened with organism size, possibly because larger organisms are both less plastic in their fundamental niches and more able to be selective in dispersal. These results suggest that the relative importance of deterministic and stochastic processes may be predictable from organism size.
The reduced expression of solute carrier family 2, facilitated glucose transporter member 4 (GLUT4) and hexokinase-2 (HK2) in skeletal muscle participates in insulin resistance of diabetes mellitus ...(DM). MicroRNAs (miRNAs) have emerged as important modulators of mRNA/protein expression, but their role in DM is unclear. We investigated miRNAs hypothetically involved in GLUT4/HK2 expression in soleus muscle of type 1 diabetes-like rats.
analysis revealed 651 miRNAs predicted to regulate
(
) mRNA, several of them also predicted to regulate
mRNA, and 16 miRNAs were selected for quantification. Diabetes reduced
/GLUT4 and
/HK2 expression (50-77%), upregulated miR-29b-3p and miR-29c-3p (50-100%), and downregulated miR-93-5p, miR-150-5p, miR-199a-5p, miR-345-3p, and miR-532-3p (~30%) expression. Besides, GLUT4 and HK2 proteins correlated (
< 0.05) negatively with miR-29b-3p and miR-29c-3p and positively with miR-199a-5p and miR-532-3p, suggesting that these miRNAs could be markers of alterations in GLUT4 and HK2 expression. Additionally, diabetes increased the nuclear factor kappa B subunit 1 protein (p50) expression, a repressor of
, which was also predicted as a target for miR-199a-5p and miR-532-3p. Correlations were also detected between these miRNAs and blood glucose, 24-h glycosuria and plasma fructosamine, and insulin therapy reversed most of the alterations. In sum, we report that diabetes altered miR-29b-3p, miR-29c-3p, miR-199a-5p and miR-532-3p expression in muscle of male rats, where their predicted targets
/GLUT4 and
/HK2 are repressed. These data shed light on these miRNAs as a markers of impaired skeletal muscle glucose disposal, and, consequently, glycemic control in diabetes.
The strategies adopted by viruses to reprogram the translation and protein quality control machinery and promote infection are poorly understood. Here, we report that the viral ubiquitin deconjugase ...(vDUB)-encoded in the large tegument protein of Epstein-Barr virus (EBV BPLF1)-regulates the ribosomal quality control (RQC) and integrated stress responses (ISR). The vDUB participates in protein complexes that include the RQC ubiquitin ligases ZNF598 and LTN1. Upon ribosomal stalling, the vDUB counteracts the ubiquitination of the 40 S particle and inhibits the degradation of translation-stalled polypeptides by the proteasome. Impairment of the RQC correlates with the readthrough of stall-inducing mRNAs and with activation of a GCN2-dependent ISR that redirects translation towards upstream open reading frames (uORFs)- and internal ribosome entry sites (IRES)-containing transcripts. Physiological levels of active BPLF1 promote the translation of the EBV Nuclear Antigen (EBNA)1 mRNA in productively infected cells and enhance the release of progeny virus, pointing to a pivotal role of the vDUB in the translation reprogramming that enables efficient virus production.
Snakes have provided a serious threat to primates throughout evolution. Furthermore, bites by venomous snakes still cause significant morbidity and mortality in tropical regions of the world. ...According to the Snake Detection Theory (SDT Isbell, 2006; 2009), the vital need to detect camouflaged snakes provided strong evolutionary pressure to develop astute perceptual capacity in animals that were potential targets for snake attacks. We performed a series of behavioral tests that assessed snake detection under conditions that may have been critical for survival. We used spiders as the control stimulus because they are also a common object of phobias and rated negatively by the general population, thus commonly lumped together with snakes as "evolutionary fear-relevant". Across four experiments (N = 205) we demonstrate an advantage in snake detection, which was particularly obvious under visual conditions known to impede detection of a wide array of common stimuli, for example brief stimulus exposures, stimuli presentation in the visual periphery, and stimuli camouflaged in a cluttered environment. Our results demonstrate a striking independence of snake detection from ecological factors that impede the detection of other stimuli, which suggests that, consistent with the SDT, they reflect a specific biological adaptation. Nonetheless, the empirical tests we report are limited to only one aspect of this rich theory, which integrates findings across a wide array of scientific disciplines.
The selective release of soluble oligomeric structures from corn cobs (CC) by autohydrolysis was optimized using the severity factor (log
R
0), and a maximum xylo-oligosaccharides (XOS) production ...was obtained at log
R
0=3.75. Gel filtration chromatography was employed to separate oligosaccharides (OS) from the crude hydrolysate and two fractions with average degrees of polymerization (DP) of 3–4 and 5–6 were compared with commercial XOS in their ability to promote the growth of
Bifidobacterium adolescentis, B. longum, Lactobacillus brevis and
L. fermentum as carbon and energy sources. Among the tested strains,
B. adolescentis and
L. brevis displayed the highest growth and XOS consumption, in contrast to
B. longum and
L. fermentum whose overall growth on XOS was low. XOS mixtures from CC autohydrolysis, mainly constituted by xylotriose and xylotetraose, were fermented by
B. adolescentis as well as commercial XOS containing essentially xylobiose, whereas
L. brevis preferred XOS with an average DP of 2. However, an increase in XOS chain length to DP 5–6 clearly reduced the extension to which
B. adolescentis utilized these OS. This study showed that XOS of low molecular weight from CC autohydrolysis exhibit a potential bifidogenic capability similar to commercial XOS.
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