Evolving challenges with long-term care of liver transplant recipients.

The number of liver transplants (LT) performed worldwide continues to rise, and LT recipients are living longer post-transplant. This has led to an increasing number of LT recipients requiring lifelong care. Optimal care post-LT requires careful attention to both the allograft and systemic issues that are more common after organ transplantation. Common causes of allograft dysfunction include rejection, biliary complications, and primary disease recurrence. While immunosuppression prevents rejection and reduces incidences of some primary disease recurrence, it has detrimental systemic effects. Most commonly, these include increased incidences of metabolic syndrome, various malignancies, and infections. Therefore, it is of utmost importance to optimize immunosuppression regimens to prevent allograft dysfunction while also decreasing the risk of systemic complications. Institutional protocols to screen for systemic disease and heightened clinical suspicion also play an important role in providing optimal long-term post-LT care. In this review, we discuss these common complications of LT as well as unique considerations when caring for LT recipients in the years after transplant.

High-CO2 Levels Rather than Acidification Restrict Emiliania huxleyi Growth and Performance.

The coccolithophore Emiliania huxleyi shows a variety of responses to ocean acidification (OA) and to high-CO2 concentrations, but there is still controversy on differentiating between these two factors when using different strains and culture methods. A heavily calcified type A strain isolated from the Norwegian Sea was selected and batch cultured in order to understand whether acclimation to OA was mediated mainly by CO2 or H+, and how it impacted cell growth performance, calcification, and physiological stress management. Emiliania huxleyi responded differently to each acidification method. CO2-enriched aeration (1200 µatm, pH 7.62) induced a negative effect on the cells when compared to acidification caused by decreasing pH alone (pH 7.60). The growth rates of the coccolithophore were more negatively affected by high pCO2 than by low pH without CO2 enrichment with respect to the control (400 µatm, pH 8.1). High CO2 also affected cell viability and promoted the accumulation of reactive oxygen species (ROS), which was not observed under low pH. This suggests a possible metabolic imbalance induced by high CO2 alone. In contrast, the affinity for carbon uptake was negatively affected by both low pH and high CO2. Photochemistry was only marginally affected by either acidification method when analysed by PAM fluorometry. The POC and PIC cellular quotas and the PIC:POC ratio shifted along the different phases of the cultures; consequently, calcification did not follow the same pattern observed in cell stress and growth performance. Specifically, acidification by HCl addition caused a higher proportion of severely deformed coccoliths, than CO2 enrichment. These results highlight the capacity of CO2 rather than acidification itself to generate metabolic stress, not reducing calcification.

An analysis of the outcomes of Clostridioides difficile occurring in intestinal transplant recipients requiring hospitalization.

BACKGROUND: Organ transplantation is a known risk factor for Clostridioides difficile infection (CDI). There is limited published data on the impact of CDI in the intestinal transplant population. METHODS: We utilized the National Readmission Database (2010-2017) to study the outcomes of CDI in patients having a history of intestinal transplantation. Association of CDI with readmission and hospital resource utilization was computed in multivariable models adjusted for demographics and comorbidities. RESULTS: During 2010-2017, 8442 hospitalizations with the history of intestinal transplantation had indexed hospital admissions. Of these, 320 (3.8%) had CDI. CDI hospitalization in intestine transplant patients was associated with higher median cost $54 430 (IQR: 27 231, 109 980) as compared to patients who did not have CDI $48 888 (IQR: 22 578, 112 777), (ß: 71 814 95% confidence intervals [CI]: 676-142 953, p = .048). The median length of stay was also longer for patients with CDI 7 (IQR: 4, 13) days as compared to 5 (IQR: 3, 11) days in non-CDI (ß: 5.51 95% CI: 0.73-10.29, p = .02). The mortality rate, intestinal transplant complications, presence of malnutrition, acute kidney injury, ICU admissions, and sepsis were similar in both groups. CDI was the top cause of 30-day readmission in the intestinal transplant recipients with CDI during the index admission; the number of 30-day readmissions also increased from 2010 to 2017. CONCLUSION: CDI hospitalization in post-intestine transplant patients occurs commonly and is associated with a longer length of stay and higher costs during hospitalization. The CDI was the most common cause of readmission after the index admission of CDI in these patients.

When you need to dive in the deep end-Transplanting SARS-CoV-2 PCR+ recipients.

There is an ongoing need to understand whether transplantation during acute Coronavirus disease 2019 (COVID-19) can be performed safely, especially when urgent transplant is required. We collected retrospective data of all consecutive non-lung transplant recipients who had a positive SARS-CoV-2 polymerase chain reaction (PCR) on the day of planned deceased donor organ implantation. Data were collected from two large transplant centers from 01/01/2022 to 02/01/2023. Demographics, details regarding COVID-19 infection, waitlist priority, and details regarding transplantation were obtained. A descriptive analysis was performed. A total of 12 patients were identified: 7 renal, 4 liver, and 1 heart transplant recipient. All 12 patients were vaccinated for COVID-19. Ten were asymptomatic outpatients found positive on admission and transplanted immediately. Two were in-patients with mild COVID-19 symptoms and were reactivated on the waitlist following 3 days of remdesivir when no progression to severe COVID-19 occurred. Most patients (10/12) received remdesivir posttransplant. No complications attributed to COVID-19 were noted nor were any secondary family or healthcare worker infections observed. All recipients were managed with special isolation precautions befitting their potentially infectious state. Standard induction therapy was used in all recipients. After a median follow up period of 143 days (interquartile range: 96-201 days), 3 episodes of rejection were documented, 2/7 renal recipients experienced delayed graft function, and 2/4 liver recipients required renal replacement therapy. Graft and patient survival were 100%. Transplantation can safely proceed in select, minimally symptomatic, non-lung recipients with a positive SARS-CoV-2 PCR at the time of transplant.

Medical intestinal rehabilitation.

PURPOSE OF REVIEW: Medical intestinal rehabilitation is a part of the very complex management of patients with intestinal failure. The goal is to achieve enteral autonomy and minimize need for parenteral nutrition and hydration. In this manuscript, we will review the strategies to achieve this goal with dietary optimization and pharmacologic interventions. RECENT FINDINGS: We will review the most updated recommendations on medical management of patients with intestinal failure. SUMMARY: Medical intestinal rehabilitation is just a portion of a multistep strategy that aims to minimize need of parenteral support in patients with intestinal failure, with the ultimate goal of achieving enteral autonomy. This needs to be done by a multidisciplinary team via dietary and pharmacologic optimization.

Efficacy and safety of mammalian target of rapamycin inhibitors following intestinal and multivisceral transplantation.

This is a descriptive study reviewing the outcomes of mammalian target of rapamycin inhibitors (mTORs) in intestinal (IT) and multivisceral transplantation (MVT). This study included 22 patients, 20 adults, and two children, and an overall mean age of 46 years old at the time of transplantation. Twelve patients (54.5%) received IT, and the remainder (45.5%) MVT. The mean time between transplantation and mTORs initiation was 24 months. The indication was worsening renal function in 13 patients (59%), with 9/13 (69.2%) noted to have an increase in glomerular filtration rate of at least 10 ml/min/1.73m2 . The indication for four patients (18.2%) was a history of neuroendocrine tumor. After mTOR initiation, 50% of patients were reduced or weaned off tacrolimus and 13.7% off prednisone. mTORs were discontinued in 11/22 patients. Six patients (54.5%) stopped due to side effects, two (18.1%) for surgery, and one (9%) for acute cellular rejection. Side effects were edema (33.3%), headaches (33.3%), diarrhea (16.7%), and oral ulcers (16.7%). The average duration of mTORs prior to discontinuation due to side effects was 7 months. mTORs may function in their own niche of patients due to the potential renal safety profile, but use is most limited by tolerance to side effects.

High CO2 concentration and iron availability determine the metabolic inventory in an Emiliania huxleyi-dominated phytoplankton community.

Ocean acidification (OA), a consequence of anthropogenic carbon dioxide (CO2 ) emissions, strongly impacts marine ecosystems. OA also influences iron (Fe) solubility, affecting biogeochemical and ecological processes. We investigated the interactive effects of CO2 and Fe availability on the metabolome response of a natural phytoplankton community. Using mesocosms we exposed phytoplankton to ambient (390 µatm) or future CO2 levels predicted for the year 2100 (900 µatm), combined with ambient (4.5 nM) or high (12 nM) dissolved iron (dFe). By integrating over the whole phytoplankton community, we assigned functional changes based on altered metabolite concentrations. Our study revealed the complexity of phytoplankton metabolism. Metabolic profiles showed three stages in response to treatments and phytoplankton dynamics. Metabolome changes were related to the plankton group contributing respective metabolites, explaining bloom decline and community succession. CO2 and Fe affected metabolic profiles. Most saccharides, fatty acids, amino acids and many sterols significantly correlated with the high dFe treatment at ambient pCO2 . High CO2 lowered the abundance of many metabolites irrespective of Fe. However, sugar alcohols accumulated, indicating potential stress. We demonstrate that not only altered species composition but also changes in the metabolic landscape affecting the plankton community may change as a consequence of future high-CO2 oceans.

Effects of elevated CO2 on growth, calcification, and spectral dependence of photoinhibition in the coccolithophore Emiliania huxleyi (Prymnesiophyceae)1.

We studied the effects of elevated CO2 concentrations on cell growth, calcification, and spectral variation in the sensitivity of photosynthesis to inhibition by solar radiation in the globally important coccolithophore Emiliania huxleyi. Growth rates and chlorophyll a content per cell showed no significant differences between elevated (800 ppmv) and ambient (400 ppmv) CO2 conditions. However, the production of organic carbon and the cell quotas for both carbon and nitrogen, increased under elevated CO2 conditions, whilst particulate inorganic carbon production rates decreased under the same conditions. Biometric analyses of cells showed that coccoliths only presented significant differences due to treatments in the central area width. Most importantly, the size of the coccosphere decreased under elevated CO2 conditions. The susceptibility of photosynthesis to inhibition by ultraviolet radiation (UVR) was estimated using biological weighting functions (BWFs) and a model that predicts photosynthesis under photosynthetically active radiation and UVR exposures. BWF results demonstrated that the sensitivity of photosynthesis to UVR was not significantly different between E. huxleyi cells grown under elevated and present CO2 concentrations. We propose that the acclimation to elevated CO2 conditions involves a physiological mechanism of regulation and allocation of energy and metabolites in the cell, which is also responsible for altering the sensitivity to UVR. In coccolithophores, this mechanism might be affected by the decrease in the calcification rates.

Elevated CO2 alleviates high PAR and UV stress in the unicellular chlorophyte Dunaliella tertiolecta.

The effects of increased CO2 and irradiance on the physiological performance of the chlorophyte Dunaliella tertiolecta were studied at different PAR and UVR (UVA + UVB) irradiances, simulating the solar radiation at different depths, at present (390 ppmv, LC) and predicted CO2 levels for the year 2100 (1000 ppmv, HC). Elevated CO2 resulted in higher optimum and effective quantum yields (F(v)/F(m) and ϕPSII, respectively), electron transport rates (ETR) and specific growth rates (µ). Cell stress was alleviated in HC with respect to LC as evidenced by a decrease in reactive oxygen species (ROS) accumulation. DNA damage showed a 42-fold increase in cyclobutane-pyrimidine dimer (CPD) formation under the highest irradiance (1100 µmol quanta m(-2) s(-1)) in LC with respect to the lowest irradiance (200 µmol quanta m(-2) s(-1)). Photolyase (CII-PCD-PL) gene expression was upregulated under HC resulting in a drastic decrease in CPD accumulation to only 25% with respect to LC. Proliferating cell nuclear antigen (PCNA) accumulation was always higher in HC and the accumulation pattern indicated its involvement in repair or growth depending on the irradiance dose. The repressor of silencing (ROS1) was only marginally involved in the response, suggesting that photoreactivation was the most relevant mechanism to overcome UVR damage. Our results demonstrate that future scenarios of global change result in alleviation of irradiance stress by CO2-induced photoprotection in D. tertiolecta.

Endoscopic Surveillance of the Intestinal Allograft: Recommendations From the Intestinal Rehabilitation and Transplant Association Working Group.

Intestinal transplant (ITx) rejection lacks a reliable noninvasive biomarker and rejection surveillance relies on serial endoscopies and mucosal biopsies followed by histologic assessment. Endoscopic biopsies are also essential for identifying other ITx-related complications such as infectious, allergic, and inflammatory graft enteritis as well as post-transplant lymphoproliferative disease or graft versus host disease. In spite of its central role in ITx, published guidelines on endoscopy and biopsy are lacking and significant variability between centers in terms of timing and technical performance exists. Therefore, an international expert group convened and discussed several aspects related to the surveillance endoscopy after ITx with the aim to summarize and standardize its practice. This article summarizes these considerations on endoscopic ITx monitoring and highlights practices of surveillance and for-cause endoscopy, biopsy techniques, pathologic evaluation, potential risks and complications, outsourcing, and less-invasive monitoring techniques.

Adipogenic effect of calcium sensing receptor activation.

We established that human adipose cells and the human adipose cell line LS14 express the calcium-sensing receptor (CaSR) and that its activation induces inflammatory cytokine production. Also, its expression is enhanced upon exposure to obesity-associated proinflammatory cytokines. We have thus proposed that CaSR activation may be associated with adipose dysfunction. Here, we evaluated a possible effect on adipogenesis. We induced adipose differentiation of primary and LS14 human preadipocytes with or without the simultaneous activation of CaSR, by the exposure to the calcimimetic cinacalcet. Activation of the receptor for 24 h decreased by 40 % the early differentiation marker CCAAT/enhancer-binding protein ß. However, upon longer-term (10 day) exposure to the adipogenic cocktail, cinacalcet exerted the opposite effect, causing a dose-response increase in the expression of the mature adipose markers adipocyte protein 2, adiponectin, peroxisome proliferator-activated receptor γ, fatty acid synthase, and glycerol-3-phosphate dehydrogenase. To assess whether there was a time-sensitive effect of CaSR activation on adipogenesis, we evaluated the 10 day effect of cinacalcet exposure for the first 6, 24, 48 h, 6, and 10 days. Our observations suggest that regardless of the period of exposure, 10 day adipogenesis is elevated by cinacalcet. CaSR activation may interfere with the initial stages of adipocyte differentiation; however, these events do not seem to preclude adipogenesis from continuing. Even though adipogenesis (particularly in subcutaneous depots) is associated with insulin sensitivity and adequate adipose function, the implications of our findings in visceral adipocytes, especially in the context of inflamed AT and overnutrition, remain to be established.

Cytomegalovirus Infection Management in Multivisceral and Intestinal Transplant: A Dual Institution Study.

Intestinal transplant and multivisceral transplant were originally in pediatric populations and are relatively new procedures in adults. Despite increasing success rates in the immediate post-transplant period, infectious complications and acute and chronic rejection remain significant causes of morbidity and mortality. Previous research has shown cytomegalovirus (CMV) is the main cause of infection in this population. Due to the limited patient population, incidence of CMV viremia ranges widely and there is lack of universal protocol for treatment. This dual institution retrospective chart review between Henry Ford Hospital and Duke University analyzed adult intestinal and multivisceral transplant recipients between 2009 and 2019. Of the 32 patients identified and included in the study, 15 had CMV infection (46.9%). Of those with CMV infection, 5 (33.3%) had donor positive (D+)/recipient positive (R+) status; 5 had D-/R+; 4 had D+/R-; and one had D-/R-. There was no significant difference between mortality in those who had reported infection and not (80% vs 76.5%). The data from this study show significant rates of CMV viremia in patients undergoing intestinal transplant/multivisceral transplant with almost half of our study population having documented infection within 1 year of transplant, stressing the importance for universal protocol into CMV viremia treatment.

The First Collective Examination of Immunosuppressive Practices Among American Intestinal Transplant Centers.

Background: Unlike other solid organs, no standardized treatment algorithms exist for intestinal transplantation (ITx). We established a consortium of American ITx centers to evaluate current practices. Methods: All American centers performing ITx during the past 3 y were invited to participate. As a consortium, we generated questions to evaluate and collect data from each institution. The data were compiled and analyzed. Results: Ten centers participated, performing 211 ITx during the past 3 y (range, 3-46; mean 21.1). Induction regimens varied widely. Thymoglobulin was the most common, used in the plurality of patients (85/211; 40.3%), but there was no consensus regimen. Similarly, regimens for the treatment of acute cellular rejection, antibody-mediated rejection, and graft-versus-host disease varied significantly between centers. We also evaluated differences in maintenance immunosuppression protocols, desensitization regimens, mammalian target of rapamycin use, antimetabolite use, and posttransplantation surveillance practices. Maintenance tacrolimus levels, stoma presence, and scoping frequency were not associated with differences in rejection events. Definitive association between treatments and outcomes, including graft and patient survival, was not the intention of this initial collaboration and is prevented by the lack of patient-level data and the presence of confounders. However, we identified trends regarding rejection episodes after various induction strategies that require further investigation in our subsequent collaborations. Conclusions: This initial collaboration reveals the extreme heterogeneity of practices among American ITx centers. Future collaboration will explore patient-level data, stratified by age and transplant type (isolated intestine versus multivisceral), to explore the association between treatment regimens and outcomes.

Prevalence of Dental Caries in Schoolchildren from the Galapagos Islands: ESSO-Gal Cohort Report.

Objective: Dental caries remains a prevalent disease worldwide. Several epidemiological studies have shown that it affects the oral health of the pediatric population, and the Galapagos population in Ecuador is no exception. The aim of this study was to determine the prevalence of dental caries and its association, based on baseline information from the Galapagos Oral Health Study (ESSO-Gal), in children of the Galapagos Islands, Ecuador. Methods: A cross-sectional study was conducted involving 804 children aged 2-11 years. The prevalence of dental caries was assessed using the International Caries Detection and Assessment System (ICDAS II) criteria, while the presence of dental biofilm was assessed using the Silness-Löe index. Descriptive statistics, including frequency analysis and measures of central tendency and dispersion, were performed. Inferential statistical analyses were conducted to identify associations between variables. Statistical analyses were performed using the SPSS version 25.0 statistical program. Results: The caries prevalence rates based on ICDAS II codes 1-6, 1-2, and 3-6 were 98.01%, 96.9%, and 85%, respectively. A statistically significant difference was observed among the different islands regarding the cutoff point for ICDAS II codes 3-6 (p ≤ 0.001). Participants aged 6-11 years had the highest caries prevalence. Conclusions: The results show a high prevalence of dental caries among children in the Galapagos Islands, which increases with age. Contrary to expectations, the study did not find a significant correlation between the severity of dental caries and the presence of dental biofilm.

Cell survival after UV radiation stress in the unicellular chlorophyte Dunaliella tertiolecta is mediated by DNA repair and MAPK phosphorylation.

Ultraviolet radiation (UVR) induces damage in a variety of organisms, and cells may adapt by developing repair or tolerance mechanisms to counteract such damage; otherwise, the cellular fate is cell death. Here, the effect of UVR-induced cell damage and the associated signalling and repair mechanisms by which cells are able to survive was studied in Dunaliella tertiolecta. UVR did not cause cell death, as shown by the absence of SYTOX Green-positive labelling cells. Ultrastructure analysis by transmission electron microscopy demonstrated that the cells were alive but were subjected to morphological changes such as starch accumulation, chromatin disaggregation, and chloroplast degradation. This behaviour paralleled a decrease in F(v)/F(m) and the formation of cyclobutane-pyrimidine dimers, showing a 10-fold increase at the end of the time course. There was a high accumulation of the repressor of transcriptional gene silencing (ROS1), as well as the cell proliferation nuclear antigen (PCNA) in UVR-treated cells, revealing activation of DNA repair mechanisms. The degree of phosphorylation of c-Jun N-terminal kinase (JNK) and p38-like mitogen-activated protein kinases was higher in UVR-exposed cells; however, the opposite occurred with the phosphorylated extracellular signal-regulated kinase (ERK). This confirmed that both JNK and p38 need to be phosphorylated to trigger the stress response, as well as the fact that cell division is arrested when an ERK is dephosphorylated. In parallel, both DEVDase and WEHDase caspase-like enzymatic activities were active even though the cells were not dead, suggesting that these proteases must be considered within a wider frame of stress proteins, rather than specifically being involved in cell death in these organisms.

Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and the International Society for Heart and Lung Transplantation.

Advances in maintenance immunosuppression over the past three decades have improved solid organ transplantation outcomes dramatically. Uninterrupted access to immunosuppression is paramount to minimize rejection and maintain allograft and patient survival. There is no standardized approach to maintenance immunosuppression management. Agents used vary based on transplanted organ, center-specific protocol, provider expertise, insurance formularies, ability to cover co-pays, recipient characteristics and tolerability. Published data reflects this heterogeneity. Despite this limitation, maintenance immunosuppression usage cross pollinates between organ groups with standard of care agents often being used off-label, making medication access a challenge for many transplant recipients. A multidisciplinary panel of American transplant clinicians was formed to review published literature on maintenance immunosuppression with the goal to formulate consensus recommendations for their use in specific organ groups. These consensus recommendations are intended to provide transplant clinicians with a summary of literature on maintenance immunosuppression in the modern era and to support transplant team members working to secure medication access for patients.

Consensus recommendations for use of maintenance immunosuppression in solid organ transplantation: Endorsed by the American College of Clinical Pharmacy, American Society of Transplantation, and International Society for Heart and Lung Transplantation: An executive summary.

Advances in maintenance immunosuppression over the past three decades have improved solid organ transplantation outcomes dramatically. Uninterrupted access to immunosuppression is paramount to minimize rejection and maintain allograft and patient survival. Agents used vary based on transplanted organ, center-specific protocol, provider expertise, insurance formularies, ability to cover co-pays, recipient characteristics and tolerability. Published data reflects this heterogeneity. Despite these obstacles, the information about maintenance immunosuppression use cross pollinates between organ groups with standard of care agents often being used off-label, making medication access a challenge for many transplant recipients. A multidisciplinary panel of American transplant clinicians was formed to review published literature on maintenance immunosuppression with the goal to formulate consensus recommendations for their use in specific organ groups. These consensus recommendations are intended to provide transplant clinicians with a summary of literature on maintenance immunosuppression in the modern era, and to support transplant team members working to secure medication access for patients.

Different ways to die: cell death modes of the unicellular chlorophyte Dunaliella viridis exposed to various environmental stresses are mediated by the caspase-like activity DEVDase.

Programmed cell death is necessary for homeostasis in multicellular organisms and it is also widely recognized to occur in unicellular organisms. However, the mechanisms through which it occurs in unicells, and the enzymes involved within the final response is still the subject of heated debate. It is shown here that exposure of the unicellular microalga Dunaliella viridis to several environmental stresses, induced different cell death morphotypes, depending on the stimulus received. Senescent cells demonstrated classical and unambiguous apoptotic-like characteristics such as chromatin condensation, DNA fragmentation, intact organelles, and blebbing of the cell membrane. Acute heat shock caused general swelling and altered plasma membrane, but the presence of chromatin clusters and DNA strand breaks suggested a necrotic-like event. UV irradiated cells presented changes typical for necrosis, together with apoptotic characteristics resembling an intermediate cell-death phenotype termed aponecrosis-like. Cells subjected to hyperosmotic shock revealed chromatin spotting without DNA fragmentation, and extensive cytoplasmic swelling and vacuolization, comparable to a paraptotic-like cell death phenotype. Nitrogen-starved cells showed pyknosis, blebbing, and cytoplasmic consumption, indicating a similarity to autophagic/vacuolar-like cell death. The caspase-like activity DEVDase was measured by using the fluorescent substrate Ac-DEVD-AMC and antibodies against the human caspase-3 active enzyme cross-reacted with bands, the intensity of which paralleled the activity. All the environmental stresses tested produced a substantial increase in both DEVDase activity and protein levels. The irreversible caspase-3 inhibitor Z-DEVD-FMK completely inhibited the enzymatic activity whereas serine and aspartyl proteases inhibitors did not. These results show that cell death in D. viridis does not conform to a single pattern and that environmental stimuli may produce different types of cell death depending on the type and intensity of the stimulus, all of which help to understand the cell death-dependent and cell death-independent functions of caspase-like proteins. Hence, these data support the theory that alternative, non-apoptotic programmed cell death (PCDs), exist either in parallel or in an independent manner with apoptosis and were already present in single-celled organisms that evolved some 1.2-1.6 billion years ago.

Type II-Metacaspases are involved in cell stress but not in cell death in the unicellular green alga Dunaliella tertiolecta.

Ultraviolet radiation (UVR; 280-400 nm) has a great impact on aquatic ecosystems by affecting ecophysiological and biogeochemical processes as a consequence of the global change scenario generated by anthropogenic activities. We studied the effect of PAR (P)+UVA (A)+UVB (B) i.e. PAB, on the molecular physiology of the unicellular green alga Dunaliella tertiolecta for six days. We assessed the relationship between the triggered UVR stress response and metacaspases and caspase-like (CL)activities, which are proteases denoted to participate in cell death (CD) in phytoplankton. UVR inhibited cell growth and in vivo chlorophyll a fluorescence but did not cause cell death. Western blot analyses reflected that Type-II metacaspases (MCs) are present and appear to be involved in UVR induced-cell stress but not in dark-induced CD in D. tertiolecta. Enzyme kinetics revealed that cleavage of the MCs-reporter substrates RVRR, QRR, GRR, LKR, HEK, and VLK was 10-fold higher than WEHD, DEVD, IETD, and LETD CLs-substrates. The lowest apparent Michaelis-Menten constants (KM ap) corresponded to RVRRase (37.5 µM) indicating a high affinity by the RVRR substrate. The inhibition of enzymatic activities by using inhibitors with different target sites for hydrolyses demonstrated that from all of the R/ Kase activities only RVRRase was a potential candidate for being a metacaspase. In parallel, zymograms and peptide-mass fingerprinting analyses revealed the identities of such Rase activities suggesting an indirect evidence of possible natural physiological substrates of MCs. We present evidence of type II-MCs not being involved in CD in D. tertiolecta, but rather in survival strategies under the stressful irradiance conditions applied in this study.