The human cytomegalovirus (HCMV) UL78 ORF is considered to encode an orphan 7-transmembrane receptor. However, until now,
the UL78 protein (pUL78) has not been characterized. Here, we have investigated the expression of pUL78 and found it mainly
associated with the endoplasmic reticulum. However, we provide evidence that pUL78 is also localized on the cell surface from
where it is quickly endocytosed. Colocalization with adaptin and EEA-1 implies that at least a small amount of pUL78 is transported
to the trans Golgi network and early endosomes. Using a bimolecular fluorescence complementation assay and co-immunoprecipitation
experiments, we were able to find homomeric and heteromeric structure formations of pUL78 and the US28 protein, respectively.
However, the absence of pUL78 had no effect on the accumulation of inositol phosphate triggered by the US28 protein. In summary,
our results suggest that the UL78 protein of HCMV traffics between the cell surface and cytoplasm, from where it might be
recycled via early endosomes. 相似文献
The organization of the cerebral cortex into distinct modules may be described along several dimensions, most importantly, structure, connectivity and function. Identification of cortical modules by differences in whole-brain connectivity profiles derived from diffusion tensor imaging or resting state correlations has already been shown. These approaches, however, carry no task-related information. Hence, inference on the functional relevance of the ensuing parcellation remains tentative. Here, we demonstrate, that Meta-Analytic Connectivity Modeling (MACM) allows the delineation of cortical modules based on their whole-brain co-activation pattern across databased neuroimaging results. Using a model free approach, two regions of the medial pre-motor cortex, SMA and pre-SMA were differentiated solely based on their functional connectivity. Assessing the behavioral domain and paradigm class meta-data of the experiments associated with the clusters derived from the co-activation based parcellation moreover allows the identification of their functional characteristics. The ensuing hypotheses about functional differentiation and distinct functional connectivity between pre-SMA and SMA were then explicitly tested and confirmed in independent datasets using functional and resting state fMRI. Co-activation based parcellation thus provides a new perspective for identifying modules of functional connectivity and linking them to functional properties, hereby generating new and subsequently testable hypotheses about the organization of cortical modules. 相似文献
Both the corollary discharge of the oculomotor command and eye muscle proprioception provide eye position information to the brain. Two contradictory models have been suggested about how these two sources contribute to visual localization: (1) only the efference copy is used whereas proprioception is a slow recalibrator of the forward model, and (2) both signals are used together as a weighted average. We had the opportunity to test these hypotheses in a patient (R.W.) with a circumscribed lesion of the right postcentral gyrus that overlapped the human eye proprioceptive representation. R.W. was as accurate and precise as the control group (n = 19) in locating a lit LED that she viewed through the eye contralateral to the lesion. However, when the task was preceded by a brief (<1 s), gentle push to the closed eye, which perturbed eye position and stimulated eye proprioceptors in the absence of a motor command, R.W.'s accuracy significantly decreased compared with both her own baseline and the healthy control group. The data suggest that in normal conditions, eye proprioception is not used for visual localization. Eye proprioception is, however, continuously monitored to be incorporated into the eye position estimate when a mismatch with the efference copy of the motor command is detected. Our result thus supports the first model and, furthermore, identifies the limits for its operation. 相似文献
Disease prevention and health promotion programs are standardized behavioral interventions that may be combined with contextual interventions. With optimized methods, they offer proven efficacy, efficiency, transparency, manageability, and rapid transfer of knowledge.
Subject and methods
This review summarizes their central barriers and success factors based on current research.
Results
Important barriers to effective use of disease prevention and health promotion programs are low implementation fidelity, exaggerated flexibility subject to political change, inadequately trained and overworked personnel, disregard of context, change of implementation frameworks, lack of supportive contextual interventions, a plethora of programs, scarce resources and weak organizational support, resistance to social technologies, choices based on marketing criteria instead of effectiveness, and research gaps. Solutions include robust intervention plans, clear and comprehensive manuals, definition of intervention core and periphery, organizational and leadership support, qualification of users, systematic adaptation to local conditions, and quality assurance/monitoring of acceptance and effectiveness.
Conclusion
Both users and decision-makers should demand proof of effectiveness of program choices and should adhere to quality assurance procedures during implementation. Program development and evaluation should ensure (1) the definition of core intervention components, (2) instructions for adaptation of programs to specific contexts, (3) basic data on resources required for implementation, and (4) evidence of program effectiveness. 相似文献
About 20–25% of patients experience weight regain (WR) or insufficient weight loss (IWL) after bariatric metabolic surgery (BS). Therefore, we aimed to retrospectively assess the effectiveness of adjunct treatment with the GLP-1 receptor agonist semaglutide in non-diabetic patients with WR or IWL after BS.
Materials and Methods
Post-bariatric patients without type 2 diabetes (T2D) with WR or IWL (n?=?44) were included in the analysis. The primary endpoint was weight loss 3 and 6 months after initiation of adjunct treatment. Secondary endpoints included change in BMI, HbA1c, lipid profile, hs-CRP, and liver enzymes.
Results
Patients started semaglutide 64.7?±?47.6 months (mean?±?SD) after BS. At initiation of semaglutide, WR after post-bariatric weight nadir was 12.3?±?14.4% (mean?±?SD). Total weight loss during semaglutide treatment was???6.0?±?4.3% (mean?±?SD, p?<?0.001) after 3 months (3.2 months, IQR 3.0–3.5, n?=?38) and???10.3?±?5.5% (mean?±?SD, p?<?0.001) after 6 months (5.8 months, IQR 5.8–6.4, n?=?20). At 3 months, categorical weight loss was?>?5% in 61% of patients,?>?10% in 16% of patients, and?>?15% in 2% of patients. Triglycerides (OR?=?0.99; p?<?0.05), ALT (OR?=?0.87; p?=?0.05), and AST (OR?=?0.89; p?<?0.05) at baseline were negatively associated with weight loss of at least 5% at 3 months’ follow-up (p?<?0.05).
Conclusion
Treatment options to manage post-bariatric excess weight (regain) are scarce. Our results imply a clear benefit of adjunct treatment with semaglutide in post-bariatric patients. However, these results need to be confirmed in a prospective randomized controlled trial to close the gap between lifestyle intervention and revision surgery in patients with IWL or WR after BS.