Growth differentiation factor-15 (GDF-15) is a member of the TGF-
cytokine superfamily that is widely expressed and may be induced in response to tissue injury. Elevations in GDF-15 may identify a ...novel pathway involved in loss of kidney function among patients with CKD. Among participants in the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS), we tested whether kidney tissue expression of
mRNA correlates with circulating levels of GDF-15 and whether elevations in circulating GDF-15 are associated with decline in kidney function. In matching samples of 24 patients with CKD from the C-PROBE study, circulating GDF-15 levels significantly correlated with intrarenal
transcript levels (
=0.54,
=0.01). Among the 224 C-PROBE and 297 SKS participants, 72 (32.1%) and 94 (32.0%) patients, respectively, reached a composite end point of 30% decline in eGFR or progression to ESRD over a median of 1.8 and 2.0 years of follow up, respectively. In multivariable models, after adjusting for potential confounders, every doubling of GDF-15 level associated with a 72% higher (95% confidence interval, 1.21 to 4.45;
=0.003) and 65% higher (95% confidence interval, 1.08 to 2.50;
=0.02) risk of progression of kidney disease in C-PROBE and SKS participants, respectively. These results show that circulating GDF-15 levels strongly correlated with intrarenal expression of
and significantly associated with increased risk of CKD progression in two independent cohorts. Circulating GDF-15 may be a marker for intrarenal
-related signaling pathways associated with CKD and CKD progression.
Social connectedness has been linked to beneficial outcomes across domains, ages, and cultures. However, not everyone receives these benefits, as there are large individual differences in the ...capacities required to create and sustain functional interpersonal relationships. A great deal of research has been devoted to assessing and understanding these differences, often focusing on how competent interpersonal behavior renders it more likely that one will succeed interpersonally. The current paper examines five relevant approaches that have emerged from personality (global traits), social (social cognition), clinical (social skills interventions), developmental (social information processing), and industrial/organizational (situation judgment) areas of psychology. A comparison of these approaches highlights important considerations related to bandwidth and fidelity, whether the focus should be on overt behavior or underlying processes, and whether to emphasize tendencies or their effectiveness. The review concludes with calls for greater integration efforts, which can capitalize on strengths inherent to different approaches.
The calcium-selective ion channel Orai1 has a complex role in bone homeostasis, with defects in both bone production and resorption detected in Orai1 germline knock-out mice. To determine whether ...Orai1 has a direct, cell-intrinsic role in osteoblast differentiation and function, we bred Orai1 flox/flox (Orai1fl/fl) mice with Runx2-cre mice to eliminate its expression in osteoprogenitor cells. Interestingly, Orai1 was expressed in a mosaic pattern in Orai1fl/fl-Runx2-cre bone. Specifically, antibody labeling for Orai1 in vertebral sections was uniform in wild type animals, but patchy regions in Orai1fl/fl-Runx2-cre bone revealed Orai1 loss while in other areas expression persisted. Nevertheless, by micro-CT, bones from Orai1fl/fl-Runx2-cre mice showed reduced bone mass overall, with impaired bone formation identified by dynamic histomorphometry. Cortical surfaces of Orai1fl/fl-Runx2-cre vertebrae however exhibited patchy defects. In cell culture, Orai1-negative osteoblasts showed profound reductions in store-operated Ca2+ entry, exhibited greatly decreased alkaline phosphatase activity, and had markedly impaired substrate mineralization. We conclude that defective bone formation observed in the absence of Orai1 reflects an intrinsic role for Orai1 in differentiating osteoblasts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Individual differences in social relationship competence (SRC) should have significant implications for social relationship success and well-being. Ability-based measures of SRC are scarce, though, ...particularly in social-personality psychology, and these considerations led to the present research. In specific terms, a situation judgment method was used to create and examine the correlates of a scenario-based assessment of SRC termed the Social Relationship Competence–Ability Measure (SRC-AM). Four studies (total N = 994) were conducted. Study 1 used item-total correlations and factor analyses to select scenarios from a larger pool. Studies 2 and 3 then showed that the SRC-AM predicted outcomes consistent with social relationship success (Study 2) as well as psychological well-being (Study 3). Study 4, finally, linked SRC levels to peer ratings of social competence and popularity. The research highlights a class of social inferences and abilities that possess novel implications for social relationship success.
Objective
There are components of self that recognize effective courses of action and there are components of self that enact behaviors. The objective of the research was to examine alignment between ...these different components of self.
Method
The present research assessed degrees of alignment between these two components of self, in the romantic relationship domain, using scenarios involving the self and a hypothetical romantic partner, with alignment defined in terms of the extent to which self‐likelihood ratings for different courses of action (what one “would do”) correlated with the person's own effectiveness ratings (what one “should do”).
Results
In Study 1 (n = 183), this dimension of ego effectiveness positively predicted partner support and negatively predicted partner aggression, whether reported on by selves or peers. In Study 2 (n = 212), both participants and partners reported greater satisfaction in their relationships with participants scoring higher in ego effectiveness.
Conclusions
The discussion focuses both on the assessment‐related implications of the work and its relevance to understanding variations in relationship functioning.
Employees are thought to engage in deviant workplace behaviors (e.g., sabotage, theft) when they are stressed, frustrated, or angry. Given the emotional nature of these actions, individual ...differences in work-related emotional intelligence (W-EI) should, potentially, be consequential. Three studies (ns = 91, 198, & 147) examined this possibility by assessing variations in emotion perception and management skills with an ability measure specifically designed for the workplace context. Employees who received higher W-EI scores were less prone to both interpersonal deviance and organizational deviance and these relationships displayed discriminant validity as well as meaningful interactive effects with organizational stressors. The investigation extends our understanding of workplace deviance in a way that highlights an important role for work-related variations in emotional intelligence.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
An advantage of the trait approach to health is that it implicates common elements to multiple different health behaviors. An advantage of the social‐cognitive approach, in contrast, is ...that it models the situational factors that are likely to elicit particular behavioral reactions. The present research sought to combine the advantages of these two approaches.
Method
A situational judgment method was developed to quantify general variations in health competence (HC) in terms of more specific responses to simulated health‐challenging events.
Results
After developing the method, Study 1 showed that individual differences in HC were systematically related to approach‐related coping tendencies and behaviors known to be health promoting. Study 2 then showed that variations in HC predicted both health behaviors and quality of life among older individuals.
Conclusions
The results highlight a new form of HC that is not dependent on self‐reports of ability.
•Investigated romantic competence (RC) in established relationships.•High RC participants viewed relationships and their partners more favorably.•Partners characterized high RC participants as more ...supportive.•The RC levels of participants and partners were systematically correlated.•Results highlight multiple mechanisms linking RC to relationship functioning.
Romantic competence (RC) may benefit relationships, but the mechanisms responsible for such links have yet to receive sufficient attention. The present investigation assessed RC levels among participants and their romantic partners (171 couples) using a recently-developed situational judgment test and the design of the study permitted the examination of multiple pathways through which RC could benefit relationships. High RC participants generally viewed relationships in more positive terms and they were also more satisfied with their current relationships. They contributed to the relationship satisfaction of their partners through behavioral pathways and the RC levels of participants and partners were systematically correlated. Altogether, the research highlights multiple mechanisms that link romantic competence to relationship functioning.
Tyrosine sulfation is an important post-translational modification but remains difficult to detect in biological samples owing to its low stoichiometric abundance and the lack of effective enrichment ...methods. In the present study, weak anion exchange (WAX) is evaluated for the enrichment of sulfopeptides that have been modified via carbamylation to convert all primary amines to less basic carbamates. The decrease in basicity enhanced the binding of carbamylated sulfopeptides to WAX resin relative to nonsulfated peptides. Upon elution and electrospray ionization in the negative mode, ultraviolet photodissociation (UVPD) was applied for peptide sequencing. Application of the method to a tryptic digest of bovine coagulation factor V resulted in identification of sulfation on tyrosine 1513.
Continued interest in protein therapeutics has motivated the development of improved bioanalytical tools to support development programs. LC-MS offers specificity, sensitivity, and multiplexing ...capabilities without the need for target-specific reagents, making it a valuable alternative to ligand binding assays. Immunoaffinity purification (IP) and enzymatic digestion are critical, yet extensive and time-consuming components of the "gold standard" bottom-up approach to LC-MS-based protein quantitation. In the present work, commercially available technology, based on membrane-immobilized reagents in spin column and plate format, is applied to reduce IP and digestion times from hours to minutes. For a standard monoclonal antibody, the lower limit of quantitation was 0.1 ng μL
−1
compared to 0.05 ng μL
−1
for the standard method. A pharmacokinetics (PK) study dosing Herceptin in rat was analyzed by both the membrane and the standard method with a total sample processing time of 4 h and 20 h, respectively. The calculated concentrations at each time point agreed within 8% between both methods, and PK values including area under the curve (AUC), half-life (T1/2), mean residence time (MRT), clearance (CL), and volume of distribution (Vdss) agreed within 6% underscoring the utility of the membrane methodology for quantitative bioanalysis workflows.
Rapid spin membrane technology decreases the time for IP and digestion of therapeutic proteins.
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