Miracle-dz/UniFAR-FTUs huggingface dataset:
A Prohormone Convertase Cleavage Site within a Predicted α-Helix Mediates Sorting of the Neuronal and Endocrine Polypeptide VGF into the Regulated Secretory Pathway*

Distinct intracellular pathways are involved in regulated and constitutive protein secretion from neuronal and endocrine cells, yet the peptide signals and molecular mechanisms responsible for targeting and retention of soluble proteins in secretory granules are incompletely understood. By using confocal microscopy and subcellular fractionation, we examined trafficking of the neuronal and endocrine peptide precursor VGF that is stored in large dense core vesicles and undergoes regulated secretion. VGF cofractionated with secretory vesicle membranes but was not detected in detergent-resistant lipid rafts. Deletional analysis using epitope-tagged VGF suggested that the C-terminal 73-amino acid fragment of VGF, containing two predicted α-helical loops and four potential prohormone convertase (PC) cleavage sites, was necessary and sufficient with an N-terminal signal peptide-containing domain, for large dense core vesicle sorting and regulated secretion from PC12 and INS-1 cells. Further transfection analysis identified the sorting sequence as a compact C-terminal α-helix and embedded 564RRR566 PC cleavage site; mutation of the 564RRR566 PC site in VGF-(1-65): GFP:VGF-(545-617) blocked regulated secretion, whereas disruption of the α-helix had no effect. Mutation of the adjacent 567HFHH570 motif, a charged region that might enhance PC cleavage in acidic environments, also blocked regulated release. Finally, inhibition of PC cleavage in PC12 cells using the membrane-permeable synthetic peptide chloromethyl ketone (decanoyl-RVKR-CMK) blocked regulated secretion of VGF. Our studies define a critical RRR-containing C-terminal domain that targets VGF into the regulated pathway in neuronal PC12 and endocrine INS-1 cells, providing additional support for the proposed role that PCs and their cleavage sites play in regulated peptide secretion.
Efficient Cell Labelling and Path Non-existence Computation using C-obstacle Query

We present a simple algorithm to check for path non-existence for a low-degree-of-freedom (DOF) robot among static obstacles. Our algorithm is based on approximate cell decomposition of configuration space or C-space. We use C-obstacle cell query to check whether a cell lies entirely inside the C-obstacle region. This reduces the path non-existence problem to checking whether a path exists through the set of all cells that do not lie entirely inside the C-obstacle region. We present a simple and efficient algorithm to perform C-obstacle cell query using generalized penetration depth computation. Our algorithm is simple to implement and we demonstrate its performance on three-DOF and four-DOF robots.
SHIP-2 Inositol Phosphatase Is Inducibly Expressed in Human Monocytes and Serves to Regulate Fcγ Receptor-mediated Signaling*

SHIP-2, a recently identified inositol 5′-phosphatase, shares high level homology with SHIP-1. Although the role of SHIP-1 has been extensively studied, the role of SHIP-2 in myeloid cell functions is not known. Here, we have analyzed the expression patterns, molecular mechanism of activation, and function of SHIP-2 in human myeloid cell Fcγ receptor (FcγR) signaling. We report that SHIP-2 is expressed in transformed myeloid cells and in primary macrophages, but not in peripheral blood monocytes. Treatment of peripheral blood monocytes with bacterial lipopolysaccharide induced expression of SHIP-2 in a dose-dependent manner. FcγRIIa clustering in THP-1 cells induced SHIP-2 tyrosine phosphorylation, suggesting a role for SHIP-2 in modulating FcγR-mediated function. Consistent with this notion, overexpression of wild-type SHIP-2 (but not catalytically deficient SHIP-2) in THP-1 cells almost completely abrogated NFκB-mediated gene transcription in response to FcγRIIa clustering. Furthermore, FcγRIIa-induced Akt activation was blocked by wild-type SHIP-2, but not by a catalytically deficient mutant of SHIP-2. Additional experiments analyzing the molecular mechanism of SHIP-2 induction by FcγRIIa revealed that SHIP-2 associated with the phosphorylated FcγRIIa immunoreceptor tyrosine-based activation motif via the SHIP-2 SH2 domain. Thus, an SH2 domain mutant of SHIP-2 failed to associate with FcγRIIa or to become tyrosine-phosphorylated upon FcγRIIa clustering. Finally, we also demonstrate that SHIP-2 phosphorylation was induced by FcγRI clustering in THP-1 cells. These findings unravel a novel level of regulation of FcγR-mediated activation of human myeloid cells by the expression and function of the inositol phosphatase SHIP-2.
Biotic homogenization and changes in species diversity across human-modified ecosystems

Changing land use and the spread of ‘winning’ native or exotic plants are expected to lead to biotic homogenization (BH), in which previously distinct plant communities become progressively more similar. In parallel, many ecosystems have recently seen increases in local species (α-) diversity, yet γ-diversity has continued to decline at larger scales. Using national ecological surveillance data for Great Britain, we quantify relationships between change in α-diversity and between-habitat homogenizations at two levels of organization: species composition and plant functional traits. Across Britain both increases and decreases in α-diversity were observed in small random sampling plots (10–200 m2) located within a national random sample of 1 km square regions. As α-diversity declined (spatially in 1978 or temporally between 1978 and 1998), plant communities became functionally more similar, but species-compositional similarity declined. Thus, different communities converged on a narrower range of winning trait syndromes, but species identities remained historically contingent, differentiating a mosaic of residual species-poor habitat patches within each 1 km square. The reverse trends in β-diversity occurred where α-diversity increased. When impacted by the same type and intensity of environmental change, directions of change in α-diversity are likely to depend upon differences in starting productivity and disturbance. This is one reason why local diversity change and BH across habitats are not likely to be consistently coupled.
Rapid and cost-effective method for micro organism enumeration based on miniaturization of the conventional plate-counting technique

La methode classique de denombrement des micro-organismes apres culture en milieu gelose est toujours tres utilisee dans les laboratoires de microbiologie. Elle est cependant couteuse en temps et devient fastidieuse pour des etudes mettant enjeu un grand nombre d'echantillons et/ou necessitant de nombreuses repetitions. Nous avons developpe une methode miniaturisee basee sur le meme principe que la methode classique mais utilisant des plaques 96 puits pour la phase de dilution decimale des echantillons et des plaques 24 puits pour la phase d'ensemencement des dilutions dans l'agar, ceci permettant le traitement d'un grand nombre d'echantillons en gardant la meme facilite de comptage et d'interpretation des colonies. La fiabilite, la sensibilite et la reproductibilite de cette methode miniaturisee ont ete verifiees en utilisant la technique conventionnelle comme reference pour des denombrements de cellules d'Escherichia coli soumises a un traitement thermique sublethal, de bacteries lactiques au cours de la fermentation du lait en yaourt et de la flore mesophile, des coliformes totaux et de Staphylococcus aureus dans des aliments. Aucune difference significative n'a ete mise en evidence entre les resultats obtenus par les deux methodes, quels que soient les bacteries et le milieu de culture. Cette micromethode de denombrement apres culture en milieu gelose permet donc des reductions de cout et de temps de manipulation avec la meme fiabilite que la methode classique. Elle peut donc etre utile pour toutes les experiences impliquant une gamme etendue de concentrations bacteriennes ainsi qu'un grand nombre d'echantillons et de repetitions.
John Bowlby at the Tavistock

Abstract Bowlby's best know work at the Tavistock Clinic is his foundational research into attachment relationships. This paper describes his other significant contributions, as a clinician interested in family dynamics and the impact of real events in the genesis of childhood anxieties, and as an institution builder in his role in establishing a psychoanalytically based training in Child Psychotherapy oriented towards public health.
ATYPICAL LANGUAGE IN LESIONAL AND NONLESIONAL COMPLEX PARTIAL EPILEPSY

NONLESIONAL COMPLEX PARTIAL EPILEPSY To the Editor: I read the article by Gaillard et al. on the incidence of atypical handedness and language laterality in a cohort of 102 patients with epilepsy. I would like to make the following comments pertaining to their findings in table 1 and figure 1.1 The authors found an incidence of 22% for right hemisphere language laterality among their right-handed participants, calling it high and indicative of transfer of language capability from one hemisphere to the other (plasticity). However, data have indicated the presence of the same ratio of “atypical” laterality of speech in normal righthanded participants manifested in occurrences of crossed aphasia in right and left handedness.2 The logical conclusion to be drawn from this discrepancy relates to the arbitrary nature of inventory driven laterality determinations and of “thresholding” in fMRI data collection used by the authors in their study. I have also reviewed this.3,4 There is a choice in deciding on the laterality of a favorite hand in early childhood (an event long forgotten), but there is no choice as to the laterality of major hemisphere (i.e. hemisphere of action, including that of speech). Thus, since all actions start from the major hemisphere, the nondominant side lags behind the dominant by an interval equal to the interhemispheric transfer time (IHTT). 3,4 Accordingly, the best noninvasive and inexpensive test for such determinations is bimanual simultaneous drawing of a line or square with the eyes closed. The side with the longer line or larger square is contralateral to the major hemisphere. This method, first described in 1884 by Hall and Hartwell,5 is the functional equivalent of the previously described use of simple reaction time for determination of the laterality of motor control.3,4 Readers may do the same test by moving their outstretched arms to the extremes of right and left and witnessing the distance between the two index fingers, being larger on one side than the other. The side with larger distance between the two index fingers is contralateral to their major hemisphere.3–5 This corresponds to their behavioral handedness in 80 percent of cases. The remainder are those whose neural (hemispheric) and behavioral (avowed) handedness did not match.3,4
Fate of Pesticides in Soils: Toward an Integrated Approach of Influential Factors

Despite constraining legislation and increasing efficiency of pesticides (with a decrease in the applied amounts), their use still cause a contamination of environment (air, soil and water). To conciliate agricultural and environmental interests, a better understanding of the fate of pesticides is needed, in particular because it will determine the exposure and consequently the impact of pesticides on the target and non-target organisms. This goal requires new efforts of research at different scales (from molecular to field scale). Following application, most of the pesticides reach the soil either after direct application or after foliage wash-off. As a major interface between other environmental compartments, the soil plays a preponderant buffering role in the fate of pesticides. Apart volatilization, the main processes that control the fate of pesticides in soils are retention on soil particles and degradation (biotic and abiotic). These coupled bio-physico-chemical processes can lead to a transitory or permanent accumulation of pesticides in soils or, on the contrary, to their elimination from the environment. They determine the pesticide concentration in the soil solution, and have a large influence on pesticide transfer toward ground or surface waters and on their ecotoxicological impacts on soil organisms as well. The main difficulties in studying and predicting the retention and degradation of pesticides in soils are the diversity of chemical structures and reactivities of pesticides, the high diversity of soils and their heterogeneous composition and structure. In addition, the pedoclimatic conditions, in particular soil temperature and water content, have a strong influence on retention and degradation because of their effect on soil biological, chemical and physical properties. Therefore, the objective of this chapter is to provide an overview of the factors involved in the retention and degradation of pesticides in soils and to discuss and clarify the needs of new integrated approach. In particular, this work will examine (i) the pertinent scales (among elementary constituents, aggregates and mesoscopic scales) for both retention and degradation studies, (ii) the integrative properties that should be considered, such as hydrophobicity of the organo-clay granulometric fraction or soil structure, and (iii) the primordial role of water.
Molecular characterization of Giardia duodenalis from white yaks in China

Giardia duodenalis is one of the most common enteric parasites of humans and animals, including companion animals, livestock and wildlife. To date, the information about the prevalence and molecular characterization of G. duodenalis infection in white yaks was limited. In the present study, a total of 208 white yak fecal samples were collected from Tianzhu Tibetan Autonomous County (TTAC) between September 2013 and March 2014. Of the 208 white yak fecal samples, four samples (1.92%, all collected in March 2014) tested G. duodenalis-positive by PCR amplification of triosephosphate isomerase (tpi) gene. Sequence analysis confirmed the presence of G. duodenalis assemblage E. The present study revealed the presence and genotype of G. duodenalis in white yaks for the first time, and extended the host range of G. duodenalis. These results provided useful information for further genotyping or subtyping studies of G. duodenalis in white yaks.
Chronic Intestinal Pseudo-Obstruction : Antineuronal ntibody-Mediated Activation of Autophagy Via Fas

A LI M EN TA R Y TR A C T ackground & Aims: Activation of autoimmune pathays has been implicated as a contributing mechanism o the pathophysiology in some patients with chronic ntestinal pseudoobstruction (CIP). In this study we ested the hypothesis that sera from a subpopulation of atients with CIP contain autoantibodies that activate utophagy via a Fas-dependent pathway in cultured huan neuroblastoma SH-Sy5Y cells. Methods: Twentyve patients with established neurogenic CIP (20 omen, 5 men; age range, 21–57 y) were investigated nd circulating antineuronal antibodies to enteric neuons were found in 6 (24%) patients. The ability of ntineuronal antibodies to induce autophagy was ssessed using immunohistochemical, Western imunoblot, and molecular techniques. The presence f autophagosomes was monitored using a specific mmunohistochemical marker, anti–microtubulessociated light chain immunoreactivity, and colocalzation with mitochondrialand Fas-activated death omain immunofluorescence using appropriate antiodies in cells exposed to sera from matched healthy ontrols and patients with neurogenic CIP. Results: xposure of SH-Sy5Y cells to sera from patients with IP containing antineuronal antibodies revealed inreased binding of autoimmune immunoglobulin IgG class) to the surface of SH-Sy5Y cells and inreased formation of autophagosomes showing coloalization with mitochondria and Fas-activated death omain compared with control sera. Pretreatment of era with either protein L agarose beads or a soluble as receptor (extracellular domain) chimera prevented he stimulation of autophagy. Conclusions: We proide novel evidence that antineuronal antibodies may ontribute to neuronal dysfunction observed in a subset f patients with neurogenic CIP via autoantibodyediated activation of autophagy involving the Fas reeptor complex.
Bis{1-[(1H-benzotriazol-1-yl)methyl]-2-methyl-1H-imdazole-κN 3}dichloridozinc

In the mononuclear title compound, [ZnCl2(C11H11N5)2], the ZnII atom is coordinated by two Cl atoms and two imidazole N atoms in a distorted tetrahedral geometry. Adjacent complex molecules are stacked through aromatic π–π interactions; the closest distance between adjacent aromatic rings is 3.598 (2) Å.
Cloning and analysis of the gene for the major outer membrane lipoprotein from Pseudomonas aeruginosa

The gene for the Pseudomonas aeruginosa outer membrane lipoprotein I was isolated from a genomic library in the phage λ EMBL3 vector and subsequently subcloned in the low copy‐number, wide host‐range plasmid vector, pKT240. The cloned gene was highly expressed, resulting in the production of a low molecular‐weight protein (8kD) that was found to be associated with the outer membrane. Sequence anatysis showed an open reading frame of 83 amino acids with a putative N‐terminal hydrophobic signal peptide of 19 residues immediately followed by the lipoprotein consensus sequence, GLY‐CYS‐SER‐SER (residues 19–22). The predicted amino acid composition of the mature polypeptide and that of the purified lipoprotein I of P. aeruginosa (Mizuno and Kageyama, 1979) were identical. In contrast with other Gram‐negative outer membrane lipoproteins, conformation predictions suggested that the mature protein was a single alpha helix.
Differences in resistance to reinfection with low and high inocula of Trypanosoma cruzi in chagasic mice treated with nifurtimox and relation to immune response

Reinfection of chronic chagasic mice after treatment with nifurtimox resulted in different outcomes according to the number of parasites used for inoculation. Nifurtimox-treated chagasic animals injected with 2,500 trypomastigotes developed higher parasitemia and increased mortality compared with nontreated chagasic mice. When reinfection was done with 25 trypomastigotes, treated and nontreated animals showed similar parasitemias and mortalities, which were significantly higher in nonchagasic controls infected for the first time. Immunological studies showed that treatment with nifurtimox led to a decrease in anti-Trypanosoma cruzi antibodies engaged in parasite destruction, inducing either complement-dependent lysis or antibody-dependent cytotoxicity, but no difference in anti-T. cruzi cell-mediated immunity was found between treated and nontreated chagasic animals. It is concluded that treatment with nifurtimox leads to a loss of resistance to reinfection with a large number of trypanosomes, which is maintained with challenge with a few parasites, and that these two thresholds of premunition are probably associated with humoral and cell-mediated anti-T. cruzi immune responses, respectively.
Raising an ADHD child : relations between parental stress, child functional impairment, and subtypes of the disorder

Families with children that have developmental, neurological or other special care needs, typically experience high levels of stress related to raising those children (Spratt, Saylor, & Marcias, 2007). Empirical studies have shown that parents of children with learning or behavioural problems such as those present in ADHD experience higher stress levels than other parents. Parenting stress can affect not only the parent, but also the child’s functioning and the family environment. The aim of this study was to investigate how parents of children with ADHD experience stress, and where this stress might originate. More specifically, I aimed to see whether there are between-group differences in parenting stress levels in children with ADHD – Predominantly Inattentive Type and ADHD – Combined Type. A control group comprised of parents with children that have Autism. Various measures were used to examine parent’s subjective stress, depression, quality of life, resources and social support. The results of this study highlight the immense stress these families deal with and will hopefully be the first step for future preventive plans aimed at reducing stress and help families that have ADHD children.
Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration

Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70–71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions.
Bis(2-aminomethyl-1H-benzimidazole-κ2 N 2,N 3)bis(nitrato-κO)copper(II)

In the title compound, [Cu(NO3)2(C8H9N3)2], the CuII atom, lying on an inversion center, has a distorted octahedral coordination environment defined by four N atoms from two chelating 2-aminomethyl-1H-benzimidazole ligands and two O atoms from two monodentate nitrate anions. In the crystal, N—H⋯O hydrogen bonds link the complex molecules into a three-dimensional network. An intramolecular N—H⋯O hydrogen bond is also observed.