HIV-1 immune activation induces Siglec-1 expression and enhances viral trans-infection in blood and tissue myeloid cells

Background: Myeloid cells are key players in the recognition and response of the host against invading viruses. Paradoxically, upon HIV-1 infection, myeloid cells might also promote viral pathogenesis through trans-infection, a mechanism that promotes HIV-1 transmission to target cells via viral capture and storage. The receptor Siglec-1 (CD169) potently enhances HIV-1 trans-infection and is regulated by immune activating signals present throughout the course of HIV-1 infection, such as interferon α (IFNα). Results: Here we show that IFNα-activated dendritic cells, monocytes and macrophages have an enhanced ability to capture and trans-infect HIV-1 via Siglec-1 recognition of viral membrane gangliosides. Monocytes from untreated HIV-1-infected individuals trans-infect HIV-1 via Siglec-1, but this capacity diminishes after effective antiretroviral treatment. Furthermore, Siglec-1 is expressed on myeloid cells residing in lymphoid tissues, where it can mediate viral trans-infection. Conclusions: Siglec-1 on myeloid cells could fuel novel CD4+ T-cell infections and contribute to HIV-1 dissemination in vivo

THE ELEVENTH GRADE STUDENTS’ ABILITY IN USING DEMONSTRATIVE PRONOUNS AT SMA SWASTA BINA GUNA TANAH JAWA SIANTAR IN THE ACADEMIC YEAR OF 2021/2022

This study aims to determine whether students are able to use demonstrative pronouns at SMA Bina Guna Tanah Jawa Siantar. This study uses a multiple choice test design with 40 questions. The froblem of this study is the student's ability to use demonstrative pronouns. To answer the formulation of the problem related to the research objectives, the writer applies a quantitative method, namely giving tests to students and formulated in multiple choice items. Data collected through post-test consists of 34 students. The writer uses the total sample technique in this study. It means that all samples in the class are taken. The date results show that there are a total of 32% of all students' answers which can be classified as low and have not reached the minimum score, and the average score of students is 3.0 which means the category is low and students' weaknesses in using pointing pronouns are in those  because they only get 23%, the weaknesses obtained with the thesis were 25%, followed by 42%, and finally there were those who got 47%, the writer concludes that the weakness of using demonstrative pronouns is in those. Based on the findings and discussion, the researcher concluded that the students' ability to use the demonstrative pronoun method was low at SMA Bina Guna Tanah Jawa Siantar

Correlating EFL learners’ critical thinking ability and listening comprehension strategies

Even though there have been numerous studies on the use of critical thinking in language learning, research that specifically explores the relationship between critical thinking skills and listening comprehension techniques is still infrequently performed in the context of learning English in Indonesia. This study aims to reveal the correlation between EFL students' listening comprehension strategies and their critical thinking ability. Fifty Indonesian EFL students of both sexes were chosen as the study's participants to accomplish this. They were all advanced students that were chosen through cluster sampling. The Critical Thinking Questionnaire (CTQ) and the Listening Comprehension Strategies Questionnaire were the two tools used (RCSQ). On the first day, the researcher thoroughly explained the instructions for this survey and gave the participants a CTQ to assess the tactics they had used. LCSQ was delivered to them on the second day. All of the questions had to be answered within the allotted time by the participants. Fortunately, none of the students missed any of the gathered data, which will improve the accuracy of the findings. The study's conclusions showed a strong correlation between advanced EFL students' listening comprehension techniques and their capacity for critical thought. Results may be important because they help students overcome any challenges they may have with particular language abilities by identifying the tactics they use

SAMHD1's protein expression profile in humans

The deoxynucleoside triphosphate triphosphohydrolase and 3'-> 5' exonuclease SAMHD1 restricts HIV-1 infection in noncycling hematopoietic cells in vitro, and SAMHD1 mutations are associated with AGS. Little is known about the in vivo expression and functional regulation of this cellular factor. Here, we first assessed the SAMHD1 protein expression profile on a microarray of 25 human tissues from >210 donors and in purified primary cell populations. In vivo, SAMHD1 was expressed in the majority of nucleated cells of hematopoietic origin, including tissue-resident macrophages, DCs, pDCs, all developmental stages of thymic T cells, monocytes, NK cells, as well as at lower levels in B cells. Of note, SAMHD1 was abundantly expressed in HIV target cells residing in the anogenital mucosa, providing a basis for its evaluation as a cellular factor that may impact the efficiency of HIV transmission. Next, we examined the effect of the activation status and proinflammatory cytokine treatment of cells on expression and phosphorylation of SAMHD1. Activated, HIV-susceptible CD4(+) T cells carried pSAMHD1(T592), whereas resting CD4(+) T cells and macrophages expressed the unphosphorylated protein with HIV-restrictive activity. Surprisingly, stimulation of these primary cells with IFN-alpha, IFN-gamma, IL-4, IL-6, IL-12, IL-18, IL-27, or TNF-alpha affected neither SAMHD1 expression levels nor threonine 592 phosphorylation. Only IL-1 beta moderately down-regulated SAMHD1 in activated CD4(+) T cells. Taken together, this study establishes the first cross-sectional protein expression profile of SAMHD1 in human tissues and provides insight into its cell cycle-dependent phosphorylation and unresponsiveness to multiple proinflammatory cytokines

Modulation of lytic molecules restrain serial killing in γδ T lymphocytes

Abstract γδ T cells play a pivotal role in protection against various types of infections and tumours, from early childhood on and throughout life. They consist of several subsets characterised by adaptive and innate-like functions, with Vγ9Vδ2 being the largest subset in human peripheral blood. Although these cells show signs of cytotoxicity, their modus operandi remains poorly understood. Here we explore, using live single-cell imaging, the cytotoxic functions of γδ T cells upon interactions with tumour target cells with high temporal and spatial resolution. While γδ T cell killing is dominated by degranulation, the availability of lytic molecules appears tightly regulated in time and space. In particular, the limited co-occurrence of granzyme B and perforin restrains serial killing of tumour cells by γδ T cells. Thus, our data provide new insights into the cytotoxic arsenal and functions of γδ T cells, which may guide the development of more efficient γδ T cell based adoptive immunotherapies