Miracle-dz/UniFAR-FTUs huggingface dataset:
UBXD4, a UBX-Containing Protein, Regulates the Cell Surface Number and Stability of α3-Containing Nicotinic Acetylcholine Receptors

Adaptor proteins are likely to modulate spatially and temporally the trafficking of a number of membrane proteins, including neuronal nicotinic acetylcholine receptors (nAChRs). A yeast two-hybrid screen identified a novel UBX-containing protein, UBXD4, as one of the cytosolic proteins that interact directly with the α3 and α4 nAChR subunits. The function of UBX-containing proteins is largely unknown. Immunoprecipitation and confocal microscopy confirmed the interaction of UBXD4 with α3-containing nAChRs (α3* nAChRs) expressed in HEK293 cells, PC12 cells, and rat cortical neurons. Overexpression of UBXD4 in differentiated PC12 cells (dPC12) increased nAChR cell surface expression, especially that of the α3β2 subtype. These findings were corroborated by electrophysiology, immunofluorescent staining, and biotinylation of surface receptors. Silencing of UBXD4 led to a significant reduction of α3* nAChRs in rat cortical neurons and dPC12 cells. Biochemical and immunofluorescence studies of endogenous UBXD4 showed that the protein is located in both the ER and cis-Golgi compartments. Our investigations also showed that the α3 subunit is ubiquitinated and that UBXD4 can interfere with its ubiquitination and consequent degradation by the proteasome. Our data suggest that UBXD4 modulates the distribution of α3* nAChRs between specialized intracellular compartments and the plasma membrane. This effect is achieved by controlling the stability of the α3 subunit and, consequently, the number of receptors at the cell surface.
Communication intervention in Rett syndrome: a survey of speech language pathologists in Swedish health services

Abstract Purpose: To investigate communication intervention that speech language pathologists (SLPs) provide to people with Rett syndrome. Methods: A web-based survey targeting all Swedish SLPs working with people currently receiving support from habilitation services. Results: The SLPs reportedly followed recommended practice in the following aspects: (1) Information on communicative function was collected from several sources, including observation in well-known settings and reports from the client s social network, (2) Multimodal communication was promoted and, (3) Responsive partner strategies were largely targeted in the intervention. However, few instruments or standard procedures were used and partner instruction was given informally. Most SLPs used communication aids in the intervention and their general impression of using communication aids was positive. Further, augmentative and alternative communication (AAC) was estimated to increase and clarify communicative contributions from the person. Conclusions: Communication aids were reported to have a positive influence on communicative functions. Swedish SLP services followed best practice in several aspects, but there are areas with potential for development. Tools and best practice guidelines are needed to support SLPs in the AAC process for clients with Rett syndrome. Implications for Rehabilitation Communication aids were reported to increase and clarify communicative contributions from people with Rett syndrome. Systematic procedures and instruments for assessment, evaluation and partner instruction were used to a small extent. A limited range of communicative functions were targeted in the interventions. There is a need for developing best practice guidelines to support SLPs in the AAC process for this population should be clients with Rett syndrome.
Vitamin E and Risk of Type 2 Diabetes in the Women’s Health Study Randomized Controlled Trial

We directly assessed the efficacy of vitamin E supplements for primary prevention of type 2 diabetes among apparently healthy women in the Women’s Health Study randomized trial. Between 1992 and 2004, 38,716 apparently healthy U.S. women aged ≥45 years and free of diabetes, cancer, and cardiovascular disease were in two randomly assigned intervention groups and received 600 IU of vitamin E (α-tocopherol, n = 19,347) or placebo (n = 19,369) on alternate days. During a median 10-year follow-up, there were 827 cases of incident type 2 diabetes in the vitamin E group and 869 in the placebo group, a nonsignificant 5% risk reduction (relative risk [RR] 0.95 [95% CI 0.87–1.05], P = 0.31). There was no evidence that diabetes risk factors including age, BMI, postmenopausal hormone use, multivitamin use, physical activity, alcohol intake, and smoking status modified the effect of vitamin E on the risk of type 2 diabetes. In a sensitivity analysis taking compliance into account, women in the vitamin E group had an RR of 0.93 (95% CI 0.83–1.04) (P = 0.21) compared with those randomized to placebo. In this large trial with 10-year follow-up, alternate-day doses of 600 IU vitamin E provided no significant benefit for type 2 diabetes in initially healthy women.
Helping Sex Offenders to Desist Offending

In Circles of Support and Accountability (CoSA), a group of trained volunteers support sex offenders in their desistance process by engaging in a long-lasting empathic relationship. Is it safe to employ volunteers in this way? This literature review provides an overview of both theoretical explanations and empirical evidence of the possible impact of this type of volunteerism on the volunteers themselves. Fifty original research articles and reviews met the selection criteria of a systematic search. Results on effects of volunteering in general, effects of volunteer work with offenders, and effects of working with sex offenders on professionals are summarized and integrated. Generally, volunteering supports and improves physical health and mental well-being, personal growth, and citizenship. However, working with sex offenders in an empathic relationship generates both positive and negative effects on psychological and social function. Personal characteristics, task characteristics, and organizational characteristics moderate and mediate the impact.
Promoting Mental Health Help-Seeking Behavior Among First-Year College Students

ABSTRACT Awareness and utilization of mental health services on college campuses is a salient issue, particularly for first-year students as they transition into college life. The current study uses focus groups and surveys to test help-seeking messages for first-year students. In this formative research, Phase 1 focus-group participants (N = 47) discussed four message concepts related to awareness of symptoms of mental health problems and services available to students. Phase 2 participants (N = 292) viewed one of three message concepts and then completed items that measured their perceptions of the message. Focus-group results helped prioritize likely effectiveness of messages based on responses to message features and provided an understanding of mental health help-seeking perceptions among college students. The quantitative results indicate the messages have potential for increasing awareness of mental health issues, as well as promoting availability of campus resources. Implications for tailoring campaign messages to first-year students are discussed.
Relations between von Willebrand factor, markers of oxidative stress and microalbuminuria in patients with type 2 diabetes mellitus.

BACKGROUND to assess the relations among plasma levels of von Willebrand factor (vWf), microalbuminuria and markers of oxidative stress in patients with type 2 diabetes mellitus. MATERIAL/METHODS We studied 10 healthy subjects without microalbuminuria or history of coronary artery disease (CAD) and 30 patients with type 2 diabetes mellitus who were classified into three groups, each including 10 patients of matched age and sex; group 1: patients without microalbuminuria or history of CAD; group 2: patients with microalbuminuria and no history of CAD, and group 3: patients with microalbuminuria and history of CAD. All subjects underwent laboratory measurements of vWf, albumin excretion rate (AER), malondialdehyde, vitamin C, reduced glutathione and C peptide. RESULTS vWf was elevated in patients with type 2 diabetes mellitus compared with control subjects. However, levels were higher in patients with than without microalbuminuria and in patients with than without a history of CAD (96+/-12, 124+/-7, 149+/-9, 175+/-7 in the control subjects and the diabetic patients' groups respectively). There was a positive correlation between vWf and AER, MDA and C- peptide (r=0.91, 0.98, 0.96, p<0.0001) and a negative correlation between vWf and both vitamin C and reduced glutathione (r=-0.59 and -0.62 respectively, p<0.001). CONCLUSIONS vWf levels are elevated in patients with type 2 diabetes mellitus, particularly in the presence of microalbuminuria and history of CAD. vWf levels are associated with markers of increased oxidative stress and therefore reflect the severity of biochemical abnormalities, which contribute to diabetic vascular disease.
M&A Synergies and Trends in IPOs

The recent decline in IPO activity can be explained by the small firms' increasing preference for being acquired rather than growing independently. This paper sheds light on this explanation by focusing on the nature of the firms facing this decision and their potential merger synergies. First, the above explanation should be particularly true for Young Innovative Companies (YICs), which are often superior to incumbents in originating innovations but face greater difficulties in bringing them to the market. Second, a firm's trade-off between being acquired and remaining independent strongly depends on the extent of the synergies arising from a potential merger, which are however difficult to assess ex-ante. Using a new, text-based measure of business similarity as a proxy for M&A synergies, we document that YICs facing the potential to develop larger synergies are the main responsible for the decline in IPOs. Compared to 15years ago, the quarterly number of IPOs conducted by these firms has decreased by 20. At the same time, while M&A activity of other firms has declined, the number of acquisitions involving this particular type of firms has remained stable over time.
Long-term persistence of humoral and cellular immune responses induced by an AS03A-adjuvanted H1N1 2009 influenza vaccine

This manuscript presents data on the persistence of Hemagglutination Inhibition (HI) immune response against the A/California/7/2009 strain, six and 12 mo after adults received one dose (n = 138) or two doses (n = 102; 21 d apart) of a 3.75 µg Hemagglutinin antigen AS03-adjuvanted H1N1 2009 vaccine (NCT00968526). Two hundred forty subjects (18−60 y: 120; > 60 y: 120) were vaccinated. Immunogenicity end points were based on the European licensure criteria for pandemic influenza vaccines. Exploratory analyses assessed the cell-mediated immune response (CMI) up to Month 12 and the influence of previous influenza vaccination on persistence of immune response. At Month 6, the CHMP criteria were met in subjects aged 18−60 y who received one or two vaccine doses and in subjects aged > 60 y who received two vaccine doses. At Month 12, the CHMP criteria were met only in subjects aged 18−60 y who received two vaccine doses. Persistence of HI immune response against the vaccine strain was higher in subjects without prior influenza vaccination. Exploratory analyses showed that two doses of the H1N1 2009 vaccine induced persistence of H1N1-specific CD4+ T cells up to Month 6 and memory B cells up to Month 12. In conclusion, HI immune responses persisted up to 12 mo after vaccination with one-dose and two-dose regimens of the AS03-adjuvanted 3.75 µg HA H1N1 2009 pandemic influenza vaccine, although not all three CHMP guidance criteria for both groups were met at Month 6 and Month 12. The CD4+ T cell and B cell responses also persisted up to Month 12.
Multiple Novel Nonsynonymous CYP2B6 Gene Polymorphisms in Caucasians: Demonstration of Phenotypic Null Alleles

The human microsomal cytochrome P450, CYP2B6, is involved in the biotransformation of several clinically important drugs. By complete sequence analysis of the human CYP2B6 gene coding regions in selected Caucasian DNA samples, we identified the five novel missense mutations 62A>T (Q21L in exon 1), 136A>G (M46V in exon 1), 12820G>A (G99E in exon 2), 13076G>A (R140Q in exon 3), and 21388T>A (I391N in exon 8). The recently described but functionally uncharacterized variant 13072A>G (K139E) was also observed. Haplotype analysis indicated the presence of at least six novel alleles that code for the protein variants CYP2B6.10 (Q21L, R22C), CYP2B6.11 (M46V), CYP2B6.12 (G99E), CYP2B6.13 (K139E, Q172H, K262R), CYP2B6.14 (R140Q), and CYP2B6.15 (I391N). Heterologous expression in COS-1 cells revealed comparable levels of CYP2B6 apoprotein and bupropion hydroxylase activity for CYP2B6.1 (wild type) and CYP2B6.10, whereas all other variants exhibited reduced expression and/or function. The three amino acid changes M46V, G99E, and I391N resulted in almost unmeasurable (M46V) or undetectable (G99E and I391N) enzyme activity, despite the presence of residual protein. The K139E change led to completely abolished protein expression; as a consequence, no function was detected. Expression in insect cells by recombinant baculoviruses confirmed these results and demonstrated the virtual absence of incorporated heme in these protein variants. The collective allele frequency of the four very low or null activity variants M46V, G99E, K139E, and I391N was 2.6% in a Caucasian study population. These data provide further insight into the genetic variability of CYP2B6 and demonstrate the existence of phenotypic null alleles in this gene.
Cancer-mutated ribosome protein L22 (RPL22/eL22) suppresses cancer cell survival by blocking p53-MDM2 circuit

Several ribosomal proteins (RPs) in response to various ribosomal stressors have been shown to play a critical role in p53-dependent regulation of cell cycle arrest, apoptosis and tumor suppression. Here, we report ribosomal protein L22 (RPL22/eL22) as a novel p53 activator highly mutated (mostly deletion mutation) in various types of human cancers, but not essential for ribosomal biogenesis in normal cells. Ectopic expression of RPL22/eL22 suppressed the colony formation of cancer cells in a p53-dependent manner, whereas knockdown of RPL22/eL22 significantly compromised p53 activation by Actinomycin D, rescuing p53-induced G1/G0 cell cycle arrest. Interestingly, human tumors with RPL22/eL22 deletion appeared to sustain wild type p53. Mechanistically, RPL22/eL22 bound to MDM2 acidic domain and inhibited MDM2-mediated p53 ubiquitination and degradation, hence extending the half-life of p53. Ribosome-profiling analysis revealed that induction of ribosomal stress by Actinomycin D leads to the increase of ribosome-free RPL22/eL22 pool. Also, RPL22/eL22 formed a complex with MDM2/RPL5/uL18/RPL11/uL5 and synergized with RPL11/uL5 to activate p53. Furthermore, the N terminus of RPL22/eL22 bound to MDM2, while the C terminus interacted with RPL5/uL18/RPL11/uL5; both of these two fragments activated p53 by inhibiting MDM2. Our study indicates that RPL22/eL22 highly mutated in human cancers plays an anti-cancer role likely through regulation of the MDM2-p53 feedback loop, and also suggests that targeting the RPL22/eL22-MDM2-p53 pathway could be a potential strategy for future development of anti-cancer therapy.
Pmt1 mannosyl transferase is involved in cell wall incorporation of several proteins in Saccharomyces cerevisiae

We constructed hybrid proteins containing a plant α‐galactosidase fused to various C‐terminal moieties of the hypoxic Srp1p; this allowed us to identify a cell wall‐bound form of Srp1p. We showed that the last 30 amino acids of Srp1p, but not the last 16, contain sufficient information to signal glycosyl‐phosphatidylinositol anchor attachment and subsequent cell wall anchorage. The cell wall‐bound form was shown to be linked by means of a β1,6‐glucose‐containing side‐chain. Pmt1p enzyme is known as a protein‐O‐mannosyltransferase that initiates the O‐glycosidic chains on proteins. We found that a pmt1 deletion mutant was highly sensitive to zymolyase and that in this strain the α‐galactosidase–Srp1 fusion proteins, an α‐galactosidase–Sed1 hybrid protein and an α‐galactosidase–α‐agglutinin hybrid protein were absent from both the membrane and the cell wall fractions. However, the plasma membrane protein Gas1p still receives its glycosyl‐phosphatidylinositol anchor in pmt1 cells, and in this mutant strain an α‐galactosidase–Cwp2 fusion protein was found linked to the cell wall but devoid of β1,6‐glucan side‐chain, indicating an alternative mechanism of cell wall anchorage.
Alteration of the Rugose Phenotype in waaG and ddhC Mutants of Salmonella enterica Serovar Typhimurium DT104 Is Associated with Inverse Production of Curli and Cellulose

ABSTRACT The rugose (also known as wrinkled or rdar) phenotype in Salmonella enterica serovar Typhimurium DT104 Rv has been associated with cell aggregation and the ability, at low temperature under low-osmolarity conditions, to form pellicles and biofilms. Two Tn5 insertion mutations in genes that are involved in lipopolysaccharide (LPS) synthesis, ddhC (A1-8) and waaG (A1-9), of Rv resulted in diminished expression of colony rugosity. Scanning electron micrographs revealed that the ddhC mutant showed reduced amounts of extracellular matrix, while there was relatively more, profuse matrix production in the waaG mutant, compared to Rv. Both mutants appeared to produce decreased levels of curli, as judged by Western blot assays probed with anti-AgfA (curli) antibodies but, surprisingly, were observed to have increased amounts of cellulose relative to Rv. Comparison with a non-curli-producing mutant suggested that the alteration in curli production may have engendered the increased presence of cellulose. While both mutants had impaired biofilm formation when grown in rich medium with low osmolarity, they constitutively formed larger amounts of biofilms when the growth medium was supplemented with either glucose or a combination of glucose and NaCl. These observations indicated that LPS alterations may have opposing effects on biofilm formation in these mutants, depending upon either the presence or the absence of these osmolytes. The phenotypes of the waaG mutant were further confirmed in a constructed, nonpolar deletion mutant of S. enterica serovar Typhimurium LT2, where restoration to the wild-type phenotypes was accomplished by complementation. These results highlight the importance of an integral LPS, at both the O-antigen and core polysaccharide levels, in the modulation of curli protein and cellulose production, as well as in biofilm formation, thereby adding another potential component to the complex regulatory system which governs multicellular behaviors in S. enterica serovar Typhimurium.
Superoxide Dismutase: A POSSIBLE PROTECTIVE ENZYME AGAINST OZONE INJURY IN SNAP BEANS (PHASEOLUS VULGARIS L.).

An experimental chemical N-[2-(2-oxo-1-imidazolidinyl)ethyl]-N'-phenylurea (EDU), is an effective protectant against acute and chronic foliar injury due to ozone (0(3)) when sprayed on intact leaves or supplied to the plants through soil application. An 0(3)-sensitive snap bean cultivar (Phaseolus vulgaris L. ;Bush Blue Lake 290') was systemically treated with EDU (0, 25, 50, and 100 milligrams per 15-centimeter diameter pot) to determine if EDU-induced or activated protective oxyradical and peroxyl scavenging enzymes. EDU-enhanced tolerance to O(3) injury always correlated with increases in superoxide dismutase (SOD) and catalase activities in the leaves. Peroxidase levels correlated more closely with foliar injury. Greater SOD levels in young leves compared to older leaves were associated with lower ozone sensitivities in these tissues.Polyacrylamide slab gel electrophoresis separations and specific determinations of SOD activity showed that EDU-treated plants possessed markedly greater SOD activity than non-treated plants. Tolerant plant tissues may have enhanced enzyme scavenging capabilities for the protection against toxic oxyradicals. Experimental confirmation for the oxyradical theory for O(3) phytotoxicity and SOD involvement in the detoxification process are presented.
Concreteness effects in semantic processing: ERP evidence supporting dual-coding theory.

Dual-coding theory argues that processing advantages for concrete over abstract (verbal) stimuli result from the operation of 2 systems (i.e., imaginal and verbal) for concrete stimuli, rather than just 1 (for abstract stimuli). These verbal and imaginal systems have been linked with the left and right hemispheres of the brain, respectively. Context-availability theory argues that concreteness effects result from processing differences in a single system. The merits of these theories were investigated by examining the topographic distribution of event-related brain potentials in 2 experiments (lexical decision and concrete-abstract classification). The results were most consistent with dual-coding theory. In particular, different scalp distributions of an N400-like negativity were elicited by concrete and abstract words.
Coexpression of Y1, Y2, and Y4 Receptors in Smooth Muscle Coupled to Distinct Signaling Pathways

Coexpression of Y1, Y2, and Y4 receptors on smooth muscle cells was determined by reverse transcription-polymerase chain reaction, and the receptors were characterized by radioligand binding, selective receptor protection, and functional analysis of signaling pathways. 125I-peptide YY (PYY) binding was completely inhibited by neuropeptide Y (NPY) and PYY, and partially inhibited by the Y1 agonist [Leu31, Pro34]NPY or the Y2 agonist NPY13–36. In cells where Y1 receptors were preserved by selective receptor protection, 125I-PYY binding was selectively inhibited by the Y1 agonist or antagonist BIBP 3226 [(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-d-arginine-amide]. Conversely, in cells where Y2 receptors were preserved, 125I-PYY binding was selectively inhibited by the Y2 agonist or antagonist BIIE 0246 [(S)N2-[1-[2-[4-[(R,S)-5,11-dihydro-6(66H)-oxodibenz[b,e]azepin-11-y]-1piperazinyl]-2-oxoethyl]cyclopentyl]acetyl]-N-[2-[1,2-dihydro-35(4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]-argininamide]. All Y receptors activated preferentially Gi2, but only Y2 and Y4 receptors activated Gq. Consequently, Y2 agonists (NPY, PYY, and NPY13–36) and the Y4 agonist (pancreatic polypeptide) induced concentration-dependent contraction, inositol 1,4,5-trisphosphate (IP3) formation, and increase in cytosolic free Ca2+. Contraction induced by Y2 and Y4 agonists was not affected by 0 Ca2+, Ca2+ channel blockers, or pertussis toxin (PTx), but it was abolished by thapsigargin, U73122 [1-(6-(17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-25-dione], or the myosin light chain kinase inhibitor ML-9 [1-(5-chloronaphthalene-1-sulfonyl)homopiperazine, HCl]. Y2-mediated contraction was inhibited by the selective Y2 antagonist BIIE 0246. Insensitivity to PTx implied that the coupling to Gi did not initiate (Y1) or contribute (Y2 and Y4) to contraction. All Y receptor agonists inhibited cAMP formation in a PTx-sensitive manner. The patterns of contraction and inhibition of cAMP by various Y receptors were corroborated by selective receptor protection. The study demonstrates coexpression of Y1, Y2, and Y4 receptors on smooth muscle negatively coupled to adenylyl cyclase via Gi2. Coupling of Y2 and Y4 receptors to Gq determines their ability to induce IP3-dependent Ca2+ release and initiate contraction.