Impedance matching in optically induced dielectrophoresis: Effect of medium conductivity on trapping force.

An impedance analysis for optically induced dielectrophoresis is presented. A circuit model is developed for this purpose. The model parameters are fully defined in terms of the geometrical and material properties of the system. It is shown that trapping force can only be generated when the material properties follow certain impedance matching conditions. The impedance match factor is introduced to succinctly quantify the phenomenon. It is used to calculate bounds on the allowed electrical conductivity of the suspension medium. Results from the proposed model are found to be in good agreement with full-wave numerical simulations. By computing the acceptable set of material parameters with little computational cost, the presented analysis can streamline ODEP system design for various applications.

Interleukin-21 engineering enhances NK cell activity against glioblastoma via CEBPD.

Glioblastoma (GBM) is an aggressive brain cancer with limited therapeutic options. Natural killer (NK) cells are innate immune cells with strong anti-tumor activity and may offer a promising treatment strategy for GBM. We compared the anti-GBM activity of NK cells engineered to express interleukin (IL)-15 or IL-21. Using multiple in vivo models, IL-21 NK cells were superior to IL-15 NK cells both in terms of safety and long-term anti-tumor activity, with locoregionally administered IL-15 NK cells proving toxic and ineffective at tumor control. IL-21 NK cells displayed a unique chromatin accessibility signature, with CCAAT/enhancer-binding proteins (C/EBP), especially CEBPD, serving as key transcription factors regulating their enhanced function. Deletion of CEBPD resulted in loss of IL-21 NK cell potency while its overexpression increased NK cell long-term cytotoxicity and metabolic fitness. These results suggest that IL-21, through C/EBP transcription factors, drives epigenetic reprogramming of NK cells, enhancing their anti-tumor efficacy against GBM.

Optimizing application of dairy effluent with synthetic N fertilizer reduced nitrogen leaching in clay loam soil.

High application rates of dairy effluent and manure are often associated with nitrogen (N) leaching, which can affect groundwater quality. Here, we used a lysimeter to examine N leaching losses and biomass yield following application of dairy effluent and manure under wheat-maize cropping. The field experiment included seven treatments: no N fertilizer (Control); 200/300 kg N ha-1 synthetic N fertilizer only (wheat/maize) (CN); 100/150 kg N ha-1 synthetic N fertilizer plus 100/150 (DE1), 150/200 (DE2) and 250/350 (DE3) kg N ha-1 dairy effluent; 100/150 kg N ha-1 synthetic fertilizer plus 100/150 kg N ha-1 dairy manure (SM1); and 150/225 kg N ha-1 synthetic fertilizer plus 50/75 kg N ha-1 dairy manure (SM2). Compared with CN, DE1 treatment increased maize yield by 10.0 %, wheat N use efficiency (NUE) by 26.5 %, and wheat and maize N uptake by 7.7-16.3 %, while reduced N leaching by 22.4 % in wheat season and by 40.4 % in the maize season. In contrast, DE2 and DE3 treatment increased N leaching by 27.2-241 % and reduced NUE by 26.2-55.2 %. SM2 treatment increased yield and NUE by 8.8 % and 7.8 %, respectively, and reduced N leaching by 42.9 % during the wheat but not the maize season. Annual N leaching losses were 37.6 kg N ha-1 under CN treatment, but decreased to 27.4 kg N ha-1 under DE1. In contrast, N leaching increased to 52.8 and 84.1 kg N ha-1 under DE2 and DE3 treatment, respectively (P < 0.05). Meanwhile, under SM1 and SM2 treatment, N leaching decreased by 71.2 % and 32.0 %, respectively, compared with CN. These results suggest that replacing 50 % and 25 % synthetic N fertilizer with dairy farm effluent and manure could reduce N leaching losses but had varied effects on crop productivity under wheat-maize cropping.

Dielectrophoretic bead-droplet reactor for solid-phase synthesis.

Solid-phase synthesis underpins many advances in synthetic and combinatorial chemistry, biology, and material science. The immobilization of a reacting species on the solid support makes interfacing of reagents an important challenge in this approach. In traditional synthesis columns, this leads to reaction errors that limit the product yield and necessitates excess consumption of the mobile reagent phase. Although droplet microfluidics can mitigate these problems, its adoption is fundamentally limited by the inability to controllably interface microbeads and reagent droplets. Here, we introduce Dielectrophoretic Bead-Droplet Reactor as a physical method to implement solid-phase synthesis on individual functionalized microbeads by encapsulating and ejecting them from microdroplets by tuning the supply voltage. Proof-of-concept demonstration of the enzymatic coupling of fluorescently labeled nucleotides onto the bead using this reactor yielded a 3.2-fold higher fidelity over columns through precise interfacing of individual microreactors and beads. Our work combines microparticle manipulation and droplet microfluidics to address a long-standing problem in solid-phase synthesis with potentially wide-ranging implications.

Distinctive expression and cellular localisation of zinc homeostasis-related proteins in breast and prostate cancer cells.

BACKGROUND: Zinc transport proteins (ZIP and ZnT), metallothioneins (MT) and protein kinase CK2 are involved in dysregulation of zinc homeostasis in breast and prostate cancer cells. Following up our previous research, we targeted ZIP12, ZnT1, MT2A and CK2 in this study by investigating their expression levels and protein localisation. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence confocal microscopy were employed to quantify the expression of ZIP12, ZnT1, MT2A and CK2 subunits in a panel of breast and prostate cell lines without or with extracellular zinc exposure. The cellular localisations of these target proteins were also examined by immunofluorescence confocal microscopy. RESULTS: In response to the extracellular zinc exposure, the gene expression was elevated for SLC39A12 (ZIP12), SLC30A1 (ZnT1) and MT2A (MT2A) in normal prostate epithelial cells (RWPE-1) in contrast to their cancerous counterparts (PC3 and DU145), whilst the gene expression was higher for SLC39A12 (ZIP12) and SLC30A1 (ZnT1) in both normal (MCF10A) and basal breast cancer cells (MDA-MB-231) compared to luminal breast cancer cells (MCF-7). At the protein level, the expression for both ZIP12 and ZnT1 was trending lower in the time course for the breast cancer cells whilst their expression was remained constant in the normal breast epithelial cells. The expression of ZIP12 in prostate cancer cells was higher than the normal prostate cells. The protein expression for CK2 α/αꞌ and CK2ß was markedly higher in prostate cancer cells than the normal prostate cells. Upon extracellular zinc exposure, ZIP12 was, for the first time, conspicuously localised in the plasma membrane of breast cancer cells but not in normal breast epithelial cells and prostate cells. ZnT1 is only localised in the plasma membrane of breast cancer cells. MT2A is distinctively seen close to the plasma membrane in breast cancer cells. CK2 is also for the first time shown to be localised in proximity to the plasma membrane of breast cancer cells. CONCLUSION: The findings, particularly the localisation of ZIP12 and CK2, are novel and significant for our understanding of zinc homeostasis in breast and prostate cancer cells.

CXCL16-dependent scavenging of oxidized lipids by islet macrophages promotes differentiation of pathogenic CD8+ T cells in diabetic autoimmunity.

The pancreatic islet microenvironment is highly oxidative, rendering ß cells vulnerable to autoinflammatory insults. Here, we examined the role of islet resident macrophages in the autoimmune attack that initiates type 1 diabetes. Islet macrophages highly expressed CXCL16, a chemokine and scavenger receptor for oxidized low-density lipoproteins (OxLDLs), regardless of autoimmune predisposition. Deletion of Cxcl16 in nonobese diabetic (NOD) mice suppressed the development of autoimmune diabetes. Mechanistically, Cxcl16 deficiency impaired clearance of OxLDL by islet macrophages, leading to OxLDL accumulation in pancreatic islets and a substantial reduction in intra-islet transitory (Texint) CD8+ T cells displaying proliferative and effector signatures. Texint cells were vulnerable to oxidative stress and diminished by ferroptosis; PD-1 blockade rescued this population and reversed diabetes resistance in NOD.Cxcl16-/- mice. Thus, OxLDL scavenging in pancreatic islets inadvertently promotes differentiation of pathogenic CD8+ T cells, presenting a paradigm wherein tissue homeostasis processes can facilitate autoimmune pathogenesis in predisposed individuals.

Spectral tweezers: Single sample spectroscopy using optoelectronic tweezers.

A scheme that combines optoelectronic tweezers (OET) with spectroscopic analysis is presented. Referred to as spectral tweezers, the approach uses a single focused light beam that acts both as the trapping beam for OET and the probe beam for spectroscopy. Having simultaneous manipulation and spectral characterization ability, the method is used to isolate single micro-samples from clusters and perform spectral measurements. Experimental results show that a characteristic spectral signature can be obtained for a given sample. The proposed approach can be easily integrated into the optical setups used for conventional OETs with only a few additional optical components, making it a convenient tool for bio-analytical applications.

Origin, spatial distribution, sediment contamination, ecological and health risk evaluation of trace metals in sediments of ship breaking area of Bangladesh.

Eleven trace metals (Cd, Cr, Fe, Mn, Cu, Ni, Co, Zn, As, Pb, and Ag) in sediments of Bangladesh's ship breaking area were measured by an atomic absorption spectrometer to determine origin, contamination extent, spatial distributions, and associated ecological and human health hazards. This study found considerable quantities of Pb, Cd, Mn, Zn, and Cu when compared with standards and high levels of Pb, Cd, Zn, Cu, As, and Ag contamination according to pollution evaluation indices. Different indices indicate most of the sampling sites were highly polluted. However, spatial distribution maps indicate that trace metals were predominantly deposited in the northern and southern region. The ecological risk index revealed that Cd has the highest while Pb and As had moderate risk. Based on the health index values, Zn for both adults and children were higher than the safe limit while Mn, Pb, Cr, As, Fe, Cu, Ni, and Co for children were close to the threshold. The mean total carcinogenic risk values of Cr, As, and Ni for children and Ni for adults exceeded the permissible threshold. The cancer risk possibilities were further assessed using Monte Carlo simulation. Most trace metals have anthropogenic origins, which were attributed to ship breaking activities.

Clinical profile and early severity predictors of dengue fever: Current trends for the deadliest dengue infection in Bangladesh in 2022.

Objectives: In 2022, Bangladesh had the highest dengue-related fatality (281). This study evaluated clinical profiles to detect early changes to predict dengue fever severity. Methods: This prospective observational study was performed in four government hospitals from June to November 2022 in Dhaka. Febrile patients admitted within 4th day of illness were recruited if they had a confirmed dengue viral infection either by by positive dengue nonstructural protein antigen or anti-dengue immunoglobulin (Ig)M antibody. Results: We divided 308 patients with confirmed dengue into two groups: 232 (74.3%) in nonsevere dengue and 76 (24.7%) in severe dengue. Men were 205 (66.6%), and the most affected age group was 21-30 years (47.7%). Patients with severe dengue reported a higher number of nausea 80.3%, coughs 57.9%, abdominal pain 56.6%, persistent vomitting 53.9%, dyspnea 35.5%, diarrhea 28.9%, and skin rash at 27.6%. In addition, the disease's febrile phase (≤4 days) showed thrombocytopenia (odds ratio [OR] 6.409, 95% CI 2.855-14.386, p <0.001), hemoconcentration (OR 3.428, 95% CI 1.030-11.405, p 0.045), and hypotension (OR 5.896, 95% CI 1.203-28.897, p 0.029) were associated severe disease. Conclusions: Hypotension, thrombocytopenia, and hemoconcentration during the febrile phase might indicate progression towards severe disease.

Microparticle electrical conductivity measurement using optoelectronic tweezers.

When it comes to simulate or calculate an optoelectronic tweezer (OET) response for a microparticle suspended in a given medium, a precise electrical conductivity (later referred to as conductivity) value for the microparticle is critical. However, there are not well-established measurements or well-referenced values for microparticle conductivities in the OET realm. Thus, we report a method based on measuring the escape velocity of a microparticle with a standard OET system to calculate its conductivity. A widely used 6 µm polystyrene bead (PSB) is used for the study. The conductivity values are found to be invariant around 2×10-3 S/m across multiple different aqueous media, which helps clarify the ambiguity in the usage of PSB conductivity. Our convenient approach could principally be applied for the measurement of multiple unknown OET-relevant material properties of microparticle-medium systems with various OET responses, which can be beneficial to carry out more accurate characterization in relevant fields.

Frequency and Factors of Sleep Paralysis Among Medical Students of Karachi.

INTRODUCTION: Sleep paralysis is a prevalent phenomenon characterized by suffocation, immobility, and hallucinations. Its causes remain unknown, although the neurotransmitter imbalance is suggested as a potential factor. This condition is closely associated with hallucinations and a sense of intrusion, often observed in patients with narcolepsy, hypertension, and seizures. METHODS: A cross-sectional study was conducted in various medical colleges in Karachi, involving 297 participants aged 18 to 30 years. The participants were divided into groups based on gender and year of study. They were surveyed about the frequency of sleep paralysis episodes, their beliefs about the phenomenon, sleep routines, and academic impacts. RESULTS: Among the respondents, a significant number of females (n=209, 70.3%) reported experiencing sleep paralysis. The overall mean age was 20±2.0 years. Correlation analysis revealed an insignificant relationship between depression and mental anxiety (p=0.147). Similarly, no significant association was found when comparing the occurrence of sleep paralysis (p=0.16). However, a notable finding was the significant link between sleep paralysis and its impact on academics (p=0.043). CONCLUSION: This study highlighted the frequency of sleep paralysis among medical students, particularly among females. Furthermore, it emphasizes the diverse beliefs held by individuals regarding these frightening episodes. To address this neglected issue, it is essential to conduct awareness sessions aimed at understanding and alleviating sleep paralysis in individuals' lives.

Novel Biomarkers and the Multiple-Marker Approach in Early Detection, Prognosis, and Risk Stratification of Cardiac Diseases: A Narrative Review.

Cardiac diseases are a primary cause of mortality worldwide, underscoring the importance of early identification and risk stratification to enhance patient outcomes. Biomarkers have become important tools for the risk assessment of cardiovascular disease and monitoring disease progression. This narrative review focuses on the multiple-marker approach, which involves simultaneously evaluating several biomarkers for the early detection and risk stratification of heart diseases. The review covers the clinical applications of novel biomarkers, such as high-sensitivity troponin, galectin-3, source of tumorigenicity 2, B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, growth differentiation factor 15, myeloperoxidase, fatty acid-binding protein, C-reactive protein, lipoprotein-associated phospholipase A2, microRNAs, circulating endothelial cells, and ischemia-modified albumin. These biomarkers have demonstrated potential in identifying people who are at high risk for developing heart disease and in providing prognostic data. Given the complexity of cardiac illnesses, the multiple-marker approach to risk assessment is extremely beneficial. Implementing the multiple-marker strategy can improve risk stratification, diagnostic accuracy, and patient care in heart disease patients.

Innovative Approaches and Therapies to Enhance Neuroplasticity and Promote Recovery in Patients With Neurological Disorders: A Narrative Review.

Brain rehabilitation and recovery for people with neurological disorders, such as stroke, traumatic brain injury (TBI), and neurodegenerative diseases, depend mainly on neuroplasticity, the brain's capacity to restructure and adapt. This literature review aims to look into cutting-edge methods and treatments that support neuroplasticity and recovery in these groups. A thorough search of electronic databases revealed a wide range of research and papers investigating several neuroplasticity-targeting methods, such as cognitive training, physical activity, non-invasive brain stimulation, and pharmaceutical interventions. The results indicate that these therapies can control neuroplasticity and improve motor, mental, and sensory function. In addition, cutting-edge approaches, such as virtual reality (VR) and brain-computer interfaces (BCIs), promise to increase neuroplasticity and foster rehabilitation. However, many issues and restrictions still need to be resolved, including the demand for individualized treatments and the absence of defined standards. In conclusion, this review emphasizes the significance of neuroplasticity in brain rehabilitation. It identifies novel strategies and treatments that promise to enhance recovery in patients with neurological illnesses. Future studies should concentrate on improving these therapies and developing evidence-based standards to direct clinical practice and enhance outcomes for this vulnerable population.

Out of the Blue: Methemoglobinemia Associated With the Use of Amyl Nitrite in Rush Poppers for Erectile Stimulation.

We report a clinical scenario involving a 51-year-old male patient with a history of prediabetes and gastritis who exhibited altered mental status following the consumption of poppers, a supplement containing nitrites, which is used for erectile stimulation. Shortly after the ingestion, the patient experienced convulsions, foaming at the mouth, and subsequently developed altered mental status and severe respiratory distress. The diagnosis of methemoglobinemia was confirmed based on elevated methemoglobin levels on venous blood gas analysis. Notably, the patient's blood had a chocolate-colored appearance upon admission, which is a characteristic finding in methemoglobinemia. Prompt recognition and management, including the administration of methylene blue, led to the resolution of symptoms. This case highlights the potential complications associated with the consumption of poppers and emphasizes the importance of early intervention.

Pathophysiology, Diagnosis, and Management of Takayasu Arteritis: A Review of Current Advances.

Takayasu arteritis (TA) is a rare, chronic, inflammatory vasculitis that primarily affects large arteries, causing significant morbidity and mortality. This review provides an overview of the pathophysiology, diagnosis, and management of TA based on current advances in the field. TA is characterized by autoimmune-mediated inflammation, vascular remodeling, and endothelial dysfunction. The disease progresses through three stages (active, chronic, and healing phase) each presenting distinct clinical features. Diagnosis of TA can be challenging due to non-specific clinical manifestations and the lack of specific diagnostic tests. Various imaging modalities, such as angiography, ultrasound, and Doppler techniques, play a crucial role in the diagnosis of TA by visualizing arterial involvement and assessing disease extent. Management of TA involves a multidisciplinary approach, with disease-modifying anti-rheumatic drugs (DMARDs) as the cornerstone of medical therapy. Synthetic and biologic DMARDs are used to induce remission, control inflammation, and prevent complications. Non-pharmacologic interventions, such as resistance exercises and curcumin supplementation, show potential benefits. Invasive interventions, including endovascular therapy and open surgery, are used for managing vascular lesions. However, challenges remain in disease understanding and management, including the heterogeneity of disease presentation and the lack of standardized treatment guidelines. The future of TA management lies in precision medicine, utilizing biomarkers and molecular profiling to personalize treatment approaches and improve patient outcomes. Further research is needed to unravel the underlying mechanisms of TA and develop targeted therapies.

Primary Cardiac Angiosarcoma: A Review.

Primary cardiac angiosarcoma is a rare and aggressive malignancy originating from the endothelial lining of cardiac blood vessels. This review covers various aspects of the disease, including its pathogenesis, clinical presentation, diagnosis, treatment, and prognosis. The primary characteristic of cardiac angiosarcoma is the rapid growth of abnormal blood vessels that invade the heart muscle, leading to the destruction of healthy tissue. Due to its infiltrative nature and early spread, diagnosing and treating cardiac angiosarcoma present significant challenges. Transesophageal echocardiography (TEE) plays a crucial role in diagnosing cardiac tumors such as angiosarcoma due to its high sensitivity. Additional imaging techniques such as computed tomography (CT) and cardiac magnetic resonance imaging (MRI) help assess tumor anatomy and identify metastases. Histopathological examination and immunohistochemistry are essential for confirming the diagnosis, as they reveal distinct histological features and specific endothelial markers associated with primary cardiac angiosarcoma. Targeted therapies directed at the angiogenic mechanisms and molecular abnormalities hold promise for improving treatment outcomes. Early detection of primary cardiac angiosarcoma remains challenging due to its rarity, and the prognosis is generally poor due to advanced disease at the time of diagnosis. The review emphasizes the importance of a multidisciplinary approach and collaboration among different specialties to optimize the diagnosis, treatment, and follow-up care of patients with primary cardiac angiosarcoma. The ultimate goal is to enhance diagnostic methods and therapeutic approaches by advancing knowledge and promoting further research into this aggressive malignancy.

Resolution improvement of optoelectronic tweezers using patterned electrodes.

An optoelectronic tweezer (OET) device is presented that exhibits improved trapping resolution for a given optical spot size. The scheme utilizes a pair of patterned physical electrodes to produce an asymmetric electric field gradient. This, in turn, generates an azimuthal force component in addition to the conventional radial gradient force. Stable force equilibrium is achieved along a pair of antipodal points around the optical beam. Unlike conventional OETs where trapping can occur at any point around the beam perimeter, the proposed scheme improves the resolution by limiting trapping to two points. The working principle is analyzed by performing numerical analysis of the electromagnetic fields and corresponding forces. Experimental results are presented that show the trapping and manipulation of micro-particles using the proposed device.

Comparative Efficacy of Direct Oral Anticoagulants and Low-Molecular-Weight Heparin in Cancer-Associated Thromboembolism: A Systematic Review and Meta-Analysis.

Patients diagnosed with cancer often experience an abnormal occurrence of venous thromboembolism (VTE) and its related complications. In order to evaluate the safety and effectiveness of both treatment approaches, we conducted a comprehensive systematic review and meta-analysis within the realm of cancer-associated thromboembolism. A thorough search was conducted across PubMed, the Cochrane Library, and Embase databases to find studies comparing direct oral anticoagulants (DOACs) with low molecular weight heparins (LMWHs) for the treatment of VTE in patients with malignancy. The analyses utilized the random-effects model. This meta-analysis included 11 studies. The results showed that DOACs were associated with a significantly reduced risk of VTE recurrence (RR: 0.67; 95% CI: 0.55, 0.81, p<0.0001; I2: 0%) and deep vein thrombosis (DVT) (RR: 0.63; 95% CI: 0.46, 0.86, p<0.0001; I2: 0%) compared to LMWHs. However, there was no significant difference in the risk of pulmonary embolism (PE) (RR: 0.76; 95% CI: 0.54, 1.06, p=0.11; I2: 11%) between the two groups. The use of DOACs was also associated with a non-significant increase in the risk of major bleeding events (RR: 1.23; 95% CI: 0.85, 1.78, p: 0.26; I2: 49%), while clinically relevant non-major bleeding (CRNMB) was significantly higher with DOACs (RR: 1.92; 95% CI: 1.11, 3.30, p: 0.02; I2: 81%). Secondary outcomes, such as survival rates and fatal PE, did not show significant differences between the two treatment groups. Our analysis indicates that direct oral anticoagulants exhibit a substantial decrease in the occurrence of VTE recurrence, deep vein thrombosis, and pulmonary embolism when compared to low molecular weight heparin in cancer-associated thromboembolism. However, it should be noted that DOACs carry a higher risk of CRNMB. Based on these findings, DOACs are recommended as a superior therapeutic option for managing cancer-associated thromboembolism compared to LMWH.

Novel Therapeutic Targets for Fibrodysplasia Ossificans Progressiva: Emerging Strategies and Future Directions.

Fibrodysplasia ossificans progressiva (FOP), also known as Stoneman syndrome, is a rare genetic disorder characterized by abnormal bone development caused by activating mutations of the ACVR1 gene. FOP affects both the developmental and postnatal stages, resulting in musculoskeletal abnormalities and heterotopic ossification. Current treatment options for FOP are limited, emphasizing the need for innovative therapeutic approaches. Challenges in the development of management criteria for FOP include difficulties in recruitment due to the rarity of FOP, disease variability, the absence of reliable biomarkers, and ethical considerations regarding placebo-controlled trials. This narrative review provides an overview of the disease and explores emerging strategies for FOP treatment. Gene therapy, particularly the CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) system, holds promise in treating FOP by specifically targeting the ACVR1 gene mutation. Another gene therapy approach being investigated is RNA interference, which aims to silence the mutant ACVR1 gene. Small molecule inhibitors targeting glycogen synthase kinase-3ß and modulation of the bone morphogenetic protein signaling pathway are also being explored as potential therapies for FOP. Stem cell-based approaches, such as mesenchymal stem cells and induced pluripotent stem cells, show potential in tissue regeneration and inhibiting abnormal bone formation in FOP. Immunotherapy and nanoparticle delivery systems provide alternative avenues for FOP treatment.

Increased Phospholipid Flux Bypasses Overlapping Essential Requirements for the Yeast Sac1p Phosphoinositide Phosphatase and ER-PM Membrane Contact Sites.

In budding yeast cells, much of the inner surface of the plasma membrane (PM) is covered with the endoplasmic reticulum (ER). This association is mediated by seven ER membrane proteins that confer cortical ER-PM association at membrane contact sites (MCSs). Several of these membrane "tether" proteins are known to physically interact with the phosphoinositide phosphatase Sac1p. However, it is unclear how or if these interactions are necessary for their interdependent functions. We find that SAC1 inactivation in cells lacking the homologous synaptojanin-like genes INP52 and INP53 results in a significant increase in cortical ER-PM MCSs. We show in sac1Δ, sac1tsinp52Δ inp53Δ, or Δ-super-tether (Δ-s-tether) cells lacking all seven ER-PM tethering genes that phospholipid biosynthesis is disrupted and phosphoinositide distribution is altered. Furthermore, SAC1 deletion in Δ-s-tether cells results in lethality, indicating a functional overlap between SAC1 and ER-PM tethering genes. Transcriptomic profiling indicates that SAC1 inactivation in either Δ-s-tether or inp52Δ inp53Δ cells induces an ER membrane stress response and elicits phosphoinositide-dependent changes in expression of autophagy genes. In addition, by isolating high-copy suppressors that rescue sac1Δ Δ-s-tether lethality, we find that key phospholipid biosynthesis genes bypass the overlapping function of SAC1 and ER-PM tethers and that overexpression of the phosphatidylserine/phosphatidylinositol-4-phosphate transfer protein Osh6 also provides limited suppression. Combined with lipidomic analysis and determinations of intracellular phospholipid distributions, these results suggest that Sac1p and ER phospholipid flux controls lipid distribution to drive Osh6p-dependent phosphatidylserine/phosphatidylinositol-4-phosphate counter-exchange at ER-PM MCSs.