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Zygnematophyceae are the algal sisters of land plants. Here we sequenced four genomes of filamentous Zygnematophyceae, including chromosome-scale assemblies for three strains of Zygnema circumcarinatum. We inferred traits in the ancestor of Zygnematophyceae and land plants that might have ushered in the conquest of land by plants: expanded genes for signaling cascades, environmental response, and multicellular growth. Zygnematophyceae and land plants share all the major enzymes for cell wall synthesis and remodifications, and gene gains shaped this toolkit. Co-expression network analyses uncover gene cohorts that unite environmental signaling with multicellular developmental programs. Our data shed light on a molecular chassis that balances environmental response and growth modulation across more than 600 million years of streptophyte evolution.

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Vimentin has been reported to play diverse roles in cell processes such as spreading, migration, cell–matrix adhesion, and fibrotic transformation. Here, we assess how vimentin impacts cell spreading, morphology, and myofibroblast transformation of human corneal fibroblasts. Overall, although knockout (KO) of vimentin did not dramatically impact corneal fibroblast spreading and mechanical activity (traction force), cell elongation in response to PDGF was reduced in vimentin KO cells as compared to controls. Blocking vimentin polymerization using Withaferin had even more pronounced effects on cell spreading and also inhibited cell-induced matrix contraction. Furthermore, although absence of vimentin did not completely block TGFβ-induced myofibroblast transformation, the degree of transformation and amount of αSMA protein expression was reduced. Proteomics showed that vimentin KO cells cultured in TGFβ had a similar pattern of protein expression as controls. One exception included periostin, an ECM protein associated with wound healing and fibrosis in other cell types, which was highly expressed only in Vim KO cells. We also demonstrate for the first time that LRRC15, a protein previously associated with myofibroblast transformation of cancer-associated fibroblasts, is also expressed by corneal myofibroblasts. Interestingly, proteins associated with LRRC15 in other cell types, such as collagen, fibronectin, β1 integrin and α11 integrin, were also upregulated. Overall, our data show that vimentin impacts both corneal fibroblast spreading and myofibroblast transformation. We also identified novel proteins that may regulate corneal myofibroblast transformation in the presence and/or absence of vimentin.

Abstract Background HIV self-testing (HIVST) has shown the potential for reaching people with heightened vulnerability to HIV, including young sexual minority men (YSMM), yet implementation of HIVST among YSMM aged 17–24 is scarce as a prevention method. Moreover, despite the consistent finding that offering HIVST increases HIV testing rates, barriers remain that need to be reduced in order to maximize the potential of this biomedical technology. Such information is necessary to direct implementation efforts to increase HIVST among YSMM, including HIV counseling and linkage to care. The current study was therefore intended to investigate perspectives for HIVST among YSMM and how HIVST can be marketed to increase implementation. Methods Between March and September 2020, we enrolled 41 YSMM to participate in one of nine online synchronous focus group discussions about their general experience with HIV preventive services. Guided by the Consolidated Framework (CFIR) for Implementation Research, we explored YSMM perspectives on facilitators and barriers to HIVST implementation. Data were analyzed using a deductive thematic content analysis approach. Results Many participants had never used HIVST before their participation in this study (n = 30; 73.2%). Qualitative results exhibited a variety of implementation determinants across the five CFIR 2.0 domains. Barriers included concerns about the format in which the testing materials would be provided (i.e., nature of packaging) and about the method in which the sample would need to be collected, particularly for those who had the testing kit mailed to their home address. These reservations were nested in the fear of unwanted disclosure of their sexual behavior, namely among the respondents who had to cohabitate with family due to the COVID-19 pandemic. Participants also discussed the limited local resources for HIVST. Many participants suggested programs that could be implemented to support HIVST, such as collaborations with trusted community agencies. Conclusions Understanding YSMM’ perspectives of HIVST may help identify implementation deficiencies within the delivery system and aid the development of implementation strategies to promote reach of HIVST.

Abstract Intramuscular cabotegravir for long-acting injectable HIV pre-exposure prophylaxis (i.e., LAI-PrEP) was approved by the U.S. FDA in 2021. We sought to explore LAI-PrEP decision-making among a nationwide sample of young sexual minority men (YSMM) 17–24 years old. In 2020, HIV-negative/unknown YSMM (n = 41) who met CDC criteria for PrEP were recruited online to participate in synchronous online focus groups eliciting preferences and opinions about LAI-PrEP, as well as the impact of a potential self-administered option. Data were analyzed using inductive and deductive thematic analysis with constant comparison. Preferences and decision-making about LAI-PrEP varied widely among YSMM, with participants frequently comparing LAI-PrEP to oral PrEP regimens. We identified five key themes related to LAI-PrEP decision-making including concerns about adherence to PrEP dosing and clinic appointments, awareness and knowledge of PrEP safety and efficacy data, comfort with needles, minimizing PrEP stigma, and considerations of self-administration. YSMM acknowledged more PrEP options as beneficial to supporting uptake and persistence.

Summary Hydrogen is a clean alternative to fossil fuels. It has applications for electricity generation and transportation and is used for the manufacturing of ammonia and steel. However, today, H2 is almost exclusively produced from coal and natural gas. As such, methods to produce H2 that do not use fossil fuels need to be developed and adopted. The biological manufacturing of H2 may be one promising solution as this process is clean and renewable. Hydrogen is produced biologically via enzymes called hydrogenases. There are three classes of hydrogenases namely [FeFe], [NiFe] and [Fe] hydrogenases. The [FeFe] hydrogenase HydA1 from the model unicellular algae Chlamydomonas reinhardtii has been studied extensively and belongs to the A1 subclass of [FeFe] hydrogenases that have the highest turnover frequencies amongst hydrogenases (21,000 ± 12,000 H2 s−1 for CaHydA from Clostridium acetobutyliticum). Yet to date, limitations in C. reinhardtii H2 production pathways have hampered commercial scale implementation, in part due to O2 sensitivity of hydrogenases and competing metabolic pathways, resulting in low H2 production efficiency. Here, we describe key processes in the biogenesis of HydA1 and H2 production pathways in C. reinhardtii. We also summarize recent advancements of algal H2 production using synthetic biology and describe valuable tools such as high‐throughput screening (HTS) assays to accelerate the process of engineering algae for commercial biological H2 production.

Objective: Seventy percent of Fuchs’ endothelial corneal dystrophy (FECD) cases are caused by an intronic trinucleotide repeat expansion in the transcription factor 4 gene (TCF4). The objective of this study was to characterize the corneal subbasal nerve plexus and corneal haze in patients with FECD with (RE+) and without the trinucleotide repeat expansion (RE−) and to assess the correlation of these parameters with disease severity. Design: Cross-sectional, single-center study. Participants: Fifty-two eyes of 29 subjects with a modified Krachmer grade of FECD severity from 1 to 6 were included in the study. Fifteen of the 29 subjects carried an expanded TCF4 allele length of ≥ 40 cytosine-thymine-guanine repeats (RE+). Main Outcomes Measures: In vivo confocal microscopy assessments of corneal nerve fiber length (CNFL), corneal nerve branch density, corneal nerve fiber density (CNFD), and anterior corneal stromal backscatter (haze); Scheimpflug tomography densitometry measurements of haze in anterior, central, and posterior corneal layers. Results: Using confocal microscopy, we detected a negative correlation between FECD severity and both CNFL and CNFD in the eyes of RE+ subjects (Spearman ρ = −0.45, P = 0.029 and ρ = −0.62, P = 0.0015, respectively) but not in the eyes of RE− subjects. Additionally, CNFD negatively correlated with the repeat length of the expanded allele in the RE+ subjects (Spearman ρ = −0.42, P = 0.038). We found a positive correlation between anterior stromal backscatter and severity in both the RE+ and RE− groups (ρ = 0.60, P = 0.0023 and ρ = 0.44, P = 0.024, respectively). The anterior, central, and posterior Scheimpflug densitometry measurements also positively correlated with severity in both the RE+ and RE− groups (P = 5.5 × 10−5, 2.5 × 10−4, and 2.9 × 10−4, respectively, after adjusting for the expansion status in a pooled analysis. However, for patients with severe FECD (Krachmer grades 5 and 6), the posterior densitometry measurements were higher in the RE+ group than in the RE− group (P < 0.05). Conclusions: Loss of corneal nerves in FECD supports the classification of the TCF4 trinucleotide repeat expansion disorder as a neurodegenerative disease. Haze in the anterior, central, and posterior cornea correlate with severity, irrespective of the genotype. Quantitative assessments of corneal nerves and corneal haze may be useful to gauge and monitor FECD disease severity in RE+ patients.

Vimentin has been reported to play diverse roles in cell processes such as spreading, migration, cell–matrix adhesion, and fibrotic transformation. Here, we assess how vimentin impacts cell spreading, morphology, and myofibroblast transformation of human corneal fibroblasts. Overall, although knockout (KO) of vimentin did not dramatically impact corneal fibroblast spreading and mechanical activity (traction force), cell elongation in response to PDGF was reduced in vimentin KO cells as compared to controls. Blocking vimentin polymerization using Withaferin had even more pronounced effects on cell spreading and also inhibited cell-induced matrix contraction. Furthermore, although absence of vimentin did not completely block TGFβ-induced myofibroblast transformation, the degree of transformation and amount of αSMA protein expression was reduced. Proteomics showed that vimentin KO cells cultured in TGFβ had a similar pattern of protein expression as controls. One exception included periostin, an ECM protein associated with wound healing and fibrosis in other cell types, which was highly expressed only in Vim KO cells. We also demonstrate for the first time that LRRC15, a protein previously associated with myofibroblast transformation of cancer-associated fibroblasts, is also expressed by corneal myofibroblasts. Interestingly, proteins associated with LRRC15 in other cell types, such as collagen, fibronectin, β1 integrin and α11 integrin, were also upregulated. Overall, our data show that vimentin impacts both corneal fibroblast spreading and myofibroblast transformation. We also identified novel proteins that may regulate corneal myofibroblast transformation in the presence and/or absence of vimentin. [ABSTRACT FROM AUTHOR]

Background With the rising toll of the opioid crisis, oculoplastic surgeons have been looking at methods to decrease opioid prescription. Objectives The aim of this study was to identify factors that correlate with opioid usage after oculoplastic surgery. Methods This was a prospective study conducted at University of Texas Southwestern. All patients who underwent an oculoplastic procedure were eligible for inclusion. Patients enrolled were provided 20 tablets of tramadol 50 mg, to take 1 tablet every 6 hours as needed for pain. At their postoperative week 1 appointment, participants had the remaining number of unused opioid tablets counted. The number of tablets taken were calculated by subtracting the remaining number of tablets from the original prescribed amount. Results A total of 310 patients were enrolled in our study. Of these, 129 patients met the inclusion criteria. There was a statistically significant difference in the number of tramadol tablets taken between procedures for upper eyelids, lower eyelids, and both eyelids (P <.01). There were no statistically significant differences in tramadol usage when comparing procedures on eyelids with orbit procedures(P =.30), cosmetic with noncosmetic procedures (P =.52), males with females (P =.87), or patients naive to oculoplastic procedures with those undergoing reoperation (P =.58). Longer procedures were correlated with greater tramadol usage (R = 0.28, P <.01). Conclusions This is the first study in the literature that has objectively quantified opioid usage after oculoplastic surgery in a prospective manner. Procedures that involve both upper and lower eyelids simultaneously and longer procedures resulted in higher opioid use. Orbital procedures, cosmetic procedures, sex, and procedural naivety were not found to be associated with higher opioid usage. Level of Evidence: 4 [ABSTRACT FROM AUTHOR]

BackgroundHIV disproportionately affects sexual minority men (SMM) in the United States. ObjectiveWe sought to determine past HIV postexposure prophylaxis (PEP) use and current and prior pre-exposure prophylaxis (PrEP) use among a web-based sample of cisgender and transgender men who have sex with men. MethodsIn 2019, HIV-negative and unknown status SMM (n=63,015) were recruited via geosocial networking apps, social media, and other web-based venues to participate in a brief eligibility screening survey. Individuals were asked about past PEP use and current and prior PrEP use. We examined associations of demographics, socioeconomic indicators, and recent club drug use with PEP and PrEP use, as well as the association between past PEP use and current and prior PrEP use using generalized linear models and multinomial logistic regression. Statistical significance was considered at P

Introduction: A large percentage of people who inject drugs (PWID) are living with HIV. Yet, rates of HIV pre-exposure prophylaxis (PrEP) use among PWID remain low. Stigma surrounding substance use and PWID have been identified as potential barriers to PrEP. This study examined healthcare providers’ concerns regarding PWID and willingness to prescribe PrEP to PWID. Methods: An online, cross-sectional survey of a diverse group of healthcare providers in the 10 U.S. cities with the greatest HIV prevalence was conducted between July 2014 and May 2015. Participants responded to a patient vignette of a PWID and asked to indicate whether the patient would be a candidate for PrEP and why via free-response text. Descriptive statistics are reported using frequency measures. Bivariate analyses were conducted using chi-squared comparisons and logistical regression. Results: Survey data from 480 providers were included in analyses. Of the 480 responses, 85.5% were classified as PrEP aware, while 14.2% were PrEP unaware. Additionally, 82.6% indicated the patient would be a good candidate for PrEP, 4.4% believed the patient was not a good candidate for PrEP, and 13% were unsure. Among those who were unsure or would not prescribe PrEP (n = 84), open-ended responses indicated lack of knowledge (42.9%), concern about adherence (27.4%), concern about cost (4.8%), and bias (7.1%) as the primary reasons. Conclusions: Although the majority of providers in this study did not demonstrate bias against PWID, our study found that limited PrEP knowledge and bias are barriers to PrEP prescription among PWID for some providers. Interventions are needed that increase PrEP awareness of CDC guidelines and reduce implicit bias among providers.

People living with HIV in rural parts of the Southern United States face poor outcomes along the HIV care continuum. Additionally, over half of people with diagnosed HIV are age 50 and older. Older adults living with HIV in the rural South often have complex health and social needs associated with HIV, aging, and the rural environment. Research is needed to understand what support organizations and clinics need in providing care to this population. This qualitative study examines the challenges health and social service providers face in caring for older patients living with HIV. In 2020–2021, we interviewed 27 key informants who work in organizations that provide care to older adults with HIV in the seven states with high rural HIV burden: Alabama, Arkansas, Kentucky, Mississippi, Missouri, Oklahoma, and South Carolina. Our findings highlight how racism and poverty; culture, politics, and religion; and a lack of healthcare infrastructure collectively shape access to HIV care for older adults in the South. Rural health and social service providers need structural-level changes to improve their care and services.