Antibodies have found applications in several fields, including, medicine, diagnostics, and nanotechnology, yet methods to modulate antibody–antigen binding using an external agent remain limited. ...Here, we have developed photoactive antibody fragments by genetic site‐specific replacement of single tyrosine residues with photocaged tyrosine, in an antibody fragment, 7D12. A simple and robust assay is adopted to evaluate the light‐mediated binding of 7D12 mutants to its target, epidermal growth factor receptor (EGFR), on the surface of cancer cells. Presence of photocaged tyrosine reduces 7D12‐EGFR binding affinity by over 20‐fold in two out of three 7D12 mutants studied, and binding is restored upon exposure to 365 nm light. Molecular dynamics simulations explain the difference in effect of photocaging on 7D12‐EGFR interaction among the mutants. Finally, we demonstrate the application of photoactive antibodies in delivering fluorophores to EGFR‐positive live cancer cells in a light‐dependent manner.
Site‐specific installation of a single photoactive amino acid in an antibody enables development of photoactive antibodies allowing light‐controlled, cell‐specific delivery of small molecules on live cancer cells.
Cytogenetic analysis of two sacral chordomas revealed two distinct abnormal clones in one of the cases: 44,XY,t(1;3)(q42;q11), -2,der(7)t(2;7)(q23;q32), -21 and 46,X,t(Y;8)(q12;q22), ...t(1;14)(p34;q32),t(5;10)(q13;p11). All cells analyzed from the second case were cytogenetically normal. To the best of our knowledge, chordomas have not previously been subjected to cytogenetic analysis.
Helpers in primitively eusocial and cooperatively breeding animal societies forfeit their own reproduction to rear the offspring of a queen or breeding pair, but may eventually attain breeding status ...themselves. Kin selection provides a widely accepted theoretical framework for understanding these societies, but differences in genetic relatedness do not explain a universal societal feature: the huge variation between individuals in helping effort. An alternative explanation for this variation lies in a fundamental trade-off faced by helpers: by working harder, they increase the indirect component of their fitness, but simultaneously decrease their own future survival and fecundity. Here, we show that individuals work less hard when they stand to lose more future fitness through working. We experimentally manipulated two components of future fitness in social queues of hover wasps (Stenogastrinae): a helper's chance of inheriting an egg-laying position, and the workforce available to rear her offspring should she inherit. After each manipulation, helpers increased or decreased their effort as appropriate to the change in expected future fitness that they experienced. Although helping provides significant indirect fitness benefits for hover wasps, our study shows that variation in the costs associated with helping is the major determinant of helping effort.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patent ductus arteriosus (PDA) is a precursor to morbidity and mortality. Percutaneous (catheter-based) closure is the procedure of choice for adults and older children with a PDA, but use during ...infancy (<1 year) is not well characterized.
Investigate the technical success and safety of percutaneous PDA closure during infancy.
Scopus, Web of Science, Embase, PubMed, and Ovid (Medline) were searched through December 2015 with no language restrictions.
Publications needed to clearly define the intervention as percutaneous PDA closure during infancy (<1 year of age at intervention) and must have reported adverse events (AEs).
The study was performed according to the Systematic Reviews and Meta-Analysis checklist and registered prospectively. The quality of the selected studies was critically examined. Data extraction and assignment of AE attributability and severity were independently performed by multiple observers. Outcomes were agreed on a priori. Data were pooled by using a random-effects model.
Thirty-eight studies were included; no randomized controlled trials were found. Technical success of percutaneous PDA closure was 92.2% (95% confidence interval CI 88.8-95.0). Overall AE and clinically significant AE incidence was 23.3% (95% CI 16.5-30.8) and 10.1% (95% CI 7.8-12.5), respectively. Significant heterogeneity and publication bias were observed.
Limitations include lack of comparative studies, lack of standardized AE reporting strategy, and significant heterogeneity in reporting.
Percutaneous PDA closure during infancy is feasible and associated with few catastrophic AEs; however, the limitations constrain the interpretability and generalizability of the current findings.
Visual perceptual learning describes the improvement of visual perception with repeated practice. Previous research has established that the learning effects of perceptual training may be ...transferable to untrained stimulus attributes such as spatial location under certain circumstances. However, the mechanisms involved in transfer have not yet been fully elucidated. Here, we investigated the effect of altering training time course on the transferability of learning effects. Participants were trained on a motion direction discrimination task or a sinusoidal grating orientation discrimination task in a single visual hemifield. The 4000 training trials were either condensed into one day, or spread evenly across five training days. When participants were trained over a five-day period, there was transfer of learning to both the untrained visual hemifield and the untrained task. In contrast, when the same amount of training was condensed into a single day, participants did not show any transfer of learning. Thus, learning time course may influence the transferability of perceptual learning effects.
“Cutaneous melanocytic tumor with CRTC1‐TRIM11 fusion” (CMTCT) is a newly described, potentially novel entity that typically presents as a dermal nodule on the head and neck, extremities, and trunk ...of adults. Histopathologically, it is reported as a nodular or multinodular tumor composed of epithelioid and spindle cells that are variably immunoreactive for S100‐protein, SOX10, and MITF along with more specific melanocytic markers such as MelanA and HMB45. With only 11 cases reported in the English literature so far, the neoplasm appears to behave in a relatively indolent fashion. Nevertheless, in one case, local recurrence and synchronous distant metastasis were evident after 13 years. Additional cases with longer follow‐up are essential to determine the neoplasm's biologic behavior with more accuracy. Herein, two cases of CMTCT, one arising on the lower back of a 65‐year‐old female and the other on the arm of a 33‐year‐old female in addition to a comprehensive literature review are reported.
Prediction of outcomes in perinatal arterial ischemic stroke (PAIS) is challenging. We performed a systematic review and meta-analysis to determine whether infarct characteristics can predict ...outcomes in PAIS.
A systematic search was conducted using five databases in January 2023. Studies were included if the sample included children with neonatal or presumed PAIS; if infarct size, location, or laterality was indicated; and if at least one motor, cognitive, or language outcome was reported. The level of evidence and risk of bias were evaluated using the Risk of Bias in Non-Randomized Studies of Interventions tool. Meta-analyses were conducted comparing infarct size or location with neurological outcomes when at least three studies could be analyzed.
Eighteen full-text articles were included in a systematic review with nine included in meta-analysis. Meta-analyses revealed that small strokes were associated with a lower risk of cerebral palsy/hemiplegia compared with large strokes (risk ratio RR = 0.263, P = 0.001) and a lower risk of epilepsy (RR = 0.182, P < 0.001). Middle cerebral artery (MCA) infarcts were not associated with a significantly different risk of cerebral palsy/hemiplegia compared with non-MCA strokes (RR = 1.220, P = 0.337). Bilateral infarcts were associated with a 48% risk of cerebral palsy/hemiplegia, a 26% risk of epilepsy, and a 58% risk of cognitive impairment.
Larger stroke size was associated with worse outcomes across multiple domains. Widely heterogeneous reporting of infarct characteristics and outcomes limits the comparison of studies and the analysis of outcomes. More consistent reporting of infarct characteristics and outcomes will be important to advance research in this field.
PDF
