Search

Serine incorporator protein 5 (SERINC5) is the host antiretroviral factor that reduces HIV-1 infectivity by incorporating into virions and inhibiting the envelope glycoprotein (Env) mediated virus fusion with target cells. We and others have shown that SERINC5 incorporation into virions alters the Env structure and sensitizes the virus to broadly neutralizing antibodies targeting cryptic Env epitopes. We have also found that SERINC5 accelerates the loss of Env function over time compared to control viruses. However, the exact mechanism by which SERINC5 inhibits HIV-1 fusion is not understood. Here, we utilized 2D and 3D super-resolution microscopy to examine the effect of SERINC5 on the distribution of Env glycoproteins on single HIV-1 particles. We find that, in agreement with a previous report, Env glycoproteins form clusters on the surface of mature virions. Importantly, incorporation of SERINC5, but not SERINC2, which lacks antiviral activity, disrupted Env clusters without affecting the overall Env content. We also show that SERINC5 and SERINC2 also form clusters on single virions. Unexpectedly, Env and SERINC molecules exhibited poor codistribution on virions, as evidenced by much greater Env-SERINC pairwise distances compared to Env-Env distances. This observation is inconsistent with the previously reported interaction between Env and SERINC5 and suggests an indirect effect of SERINC5 on Env cluster formation. Collectively, our results reveal a multifaceted mechanism of SERINC5-mediated restriction of HIV-1 fusion that, aside from the effects on individual Env trimers, involves disruption of Env clusters, which likely serve as sites of viral fusion with target cells.

Vanilla, a quintessential flavoring agent, experiences burgeoning demand globally, particularly for natural variants. In response, Taiwan has ventured into vanilla cultivation, aiming to reduce the energy consumption associated with international transportation by fostering domestic production. This study investigates the sensory attributes of Taiwan and Madagascar vanilla beans amid increasing global demand for natural vanilla. We extended our sensory evaluations to vanilla ice cream products to assess their quality. Employing sensory evaluation questionnaires and experimental techniques, we utilized purposive and snowball sampling methodologies for participant recruitment. Our primary aim is to discern the edible disparities between Taiwan and Madagascar vanilla beans by scrutinizing variations in consumer sensory preferences. Our findings reveal statistically significant disparities between Taiwan and Madagascar vanilla beans concerning product texture and overall aroma in sensory evaluations, while other attributes do not exhibit notable differences. This suggests that the sensory experience of vanilla ice cream products derived from Taiwan and Madagascar vanilla beans primarily diverges in terms of product texture and overall aroma, with negligible disparities elsewhere. Remarkably, Taiwan vanilla beans consistently outperform Madagascar vanilla beans across many evaluation criteria, underscoring the superior quality and competitive edge of Taiwan's vanilla beans. This empirical evidence highlights the exceptional quality and value proposition of Taiwan vanilla beans, offering insights for the expansion and deepening of sensory evaluations pertaining to vanilla beans. Furthermore, our study contributes to environmental sustainability by promoting local production and presents new avenues for Taiwan's vanilla processing industry. [ABSTRACT FROM AUTHOR]

Background and Objectives: Approximately 5–10% of all patients with metastatic colorectal cancer (mCRC) harbor a BRAFV600E mutation. These patients exhibit distinct metastatic patterns, poor prognosis, and heterogenous survival outcomes. The findings from the TRIBE study indicated that the administration of FOLFOXIRI plus bevacizumab as first-line treatment extended the median duration of overall survival (OS). In this study, we explored the effects of UGT1A1 polymorphism on the outcomes of irinotecan dose escalation versus FOLFOXIRI plus bevacizumab in patients with BRAFV600E-mutant mCRC. Materials and Methods: We retrospectively reviewed the medical records of 25 patients who had received a diagnosis of BRAFV600E-mutant mCRC between October 2015 and August 2022. All patients underwent UGT1A1 genotyping before receiving bevacizumab plus FOLFIRI. The primary end point was progression-free survival (PFS), and secondary endpoints were OS and adverse events (AEs). The two treatment arms were compared in terms of 6-month PFS and 12-month OS. Results: Over a median follow-up duration of 15.0 (interquartile range, 10.0–30.5) months, no significant differences were noted between the treatment arms in severe AEs (SAEs), 6-month PFS, or 12-month OS (all p < 0.05). Regarding AEs, the FOLFIRI plus bevacizumab regimen was associated with a lower incidence of anorexia than was the FOLFOXIRI plus bevacizumab regimen (p = 0.042). Conclusions: Our findings indicate that FOLFIRI plus bevacizumab with irinotecan dose escalation is an effective first-line treatment regimen for patients with BRAFV600E-mutant mCRC. This regimen leads to acceptable clinical outcomes with manageable AEs. However, the effects on survival and safety outcomes could only be speculated, and further studies are needed because of the sample size, the follow-up for the OS evaluation, and the non-uniformity in all the variables considered in the two groups. [ABSTRACT FROM AUTHOR]

A special-purpose integrated circuit that accomplishes the real-time control and filtering tasks for the JPL-Boeing micromachined gyroscopes using a flexible, low-power implementation is presented. Our exposition focuses on the integration of the circuit and a prototype sensor, the synthesis and implementation of the control filters, and the subsequent performance of the closed-loop system. Identified sensor models are also presented because the control approach and, hence, the circuit architecture, is motivated by special features of the sensor dynamics. © 2005 IEEE.

Byline: Wei-Chih. Su, Ching-Wen. Huang, Cheng-Jen. Ma, Po-Jung. Chen, Hsiang-Lin. Tsai, Tsung-Kun. Chang, Yen-Cheng. Chen, Ching-Chun. Li, Yung-Sung. Yeh, Jaw-Yuan. Wang Background: Although surgical resection is the main treatment for [...]

Sympathetic ophthalmia (SO) is a bilateral granulomatous panuveitis. We report a rare case of SO presenting after scleral necrosis as a late complication of Gamma Knife radiotherapy for choroidal melanoma. A 55-year-old woman presented with primary choroidal melanoma in the right eye and has been treated with Gamma Knife radiotherapy with stable tumor size. Five years after radiotherapy, a pigmented protrusive uveal mass was visibly noted over the superior sclera of the same eye, corresponding to periocular soft tissue enhancement on computed tomography. Biopsies of the pigmented mass showed the absence of malignancy. One month later, acute blurred vision with signs of sympathetic ophthalmia developed in the left eye. The patient received high-dose systemic corticosteroids and immunomodulatory therapy. The intraocular inflammation in the left eye subsided with improving vision, and the uveal mass in the right eye flattened after the anti-inflammatory therapy. Scleral necrosis is a rare complication following radiotherapy for choroidal melanoma and may incite sympathetic ophthalmia, for which prompt and aggressive treatment is important to save vision, especially for the fellow eye. [ABSTRACT FROM AUTHOR]