Melatonin effects on oxidative stress and on TLR4/NF-kß inflammatory pathway in the right ventricle of rats with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterised by an increase in mean pulmonary arterial pressure and a compromised the right ventricle (RV), together with progression to heart failure and premature death. Studies have evaluated the role of melatonin as a promising therapeutic strategy for PAH. The objective of this study was to evaluate melatonin's effects on oxidative stress and on the TLR4/NF-kß inflammatory pathway in the RV of rats with PAH. Male Wistar rats were divided into the following groups: control, monocrotaline (MCT), and monocrotaline plus melatonin groups. These two last groups received one intraperitoneal injection of MCT (60 mg/kg) on the first day of experimental protocol. The monocrotaline plus melatonin group received 10 mg/kg/day of melatonin by gavage for 21 days. Echocardiographic analysis was performed, and the RV was collected for morphometric analysis oxidative stress and molecular evaluations. The main findings of the present study were that melatonin administration attenuated the reduction in RV function that was induced by monocrotaline, as assessed by TAPSE. In addition, melatonin prevented RV diastolic area reduction caused by PAH. Furthermore, animals treated with melatonin did not show an increase in ROS levels or in NF-kß expression. In addition, the monocrotaline plus melatonin group showed a reduction in TLR4 expression when compared with control and monocrotaline groups. To our knowledge, this is the first study demonstrating a positive effect of melatonin on the TLR4/NF-kß pathway in the RV of rats with PAH. In this sense, this study makes it possible to think of melatonin as a possible ally in mitigating RV alterations caused by PAH.

Making waves: How to clean surface water with photogranules.

Global surface waters are in a bad ecological and chemical state, which has detrimental effects on entire ecosystems. To prevent further deterioration of ecosystems and ecosystem services, it is vital to minimize environmental pollution and come up with ways to keep surface water healthy and clean. Recently, photogranules have emerged as a promising platform for wastewater treatment to remove organic matter and nutrients with reduced or eliminated mechanical aeration, while also facilitating CO2 capture and production of various bioproducts. Photogranules are microbial aggregates of microalgae, cyanobacteria, and other non-phototrophic organisms that form dense spheroidic granules. Photogranules settle fast and can be easily retained in the treatment system, which allows increased amounts of water and wastewater to be treated. So far, photogranules have only been tested on various "high-strength" wastewaters but they might be an excellent choice for treatment of large volumes of polluted surface water as well. Here, we propose and tested for the first time photogranules on their effectiveness to remove nutrients from polluted surface water at unprecedented low concentrations (3.2 mg/L of nitrogen and 0.12 mg/L of phosphorous) and low hydraulic retention time (HRT = 1.5 h). Photogranules can successfully remove nitrogen (<0.6 mg/L, ∼80 % removal) and phosphorous (<0.01 mg/L, 90-95 % removal) to low levels in sequencing batch operation even without the need for pH control. Subjecting photogranules to surface water treatment conditions drastically changed their morphology. While, under "high-strength" conditions the photogranules were spherical, dense and defined, under polluted surface water conditions photogranules increased their surface area by forming fingers. However, this did not compromise their excellent settling properties. Finally, we discuss the future perspectives of photogranular technology for surface water treatment.

Effect of an antidepressant on aquatic ecosystems in the presence of microplastics: A mesocosm study.

Emerging pollutants, such as pharmaceuticals and microplastics have become a pressing concern due to their widespread presence and potential impacts on ecological systems. To assess the ecosystem-level effects of these pollutants within a multi-stressor context, we simulated real-world conditions by exposing a near-natural multi-trophic aquatic food web to a gradient of environmentally relevant concentrations of fluoxetine and microplastics in large mesocosms over a period of more than three months. We measured the biomass and abundance of different trophic groups, as well as ecological functions such as nutrient availability and decomposition rate. To explore the mechanisms underlying potential community and ecosystem-level effects, we also performed behavioral assays focusing on locomotion parameters as a response variable in three species: Daphnia magna (zooplankton prey), Chaoborus flavicans larvae (invertebrate pelagic predator of zooplankton) and Asellus aquaticus (benthic macroinvertebrate), using water from the mesocosms. Our mesocosm results demonstrate that presence of microplastics governs the response in phytoplankton biomass, with a weak non-monotonic dose-response relationship due to the interaction between microplastics and fluoxetine. However, exposure to fluoxetine evoked a strong non-monotonic dose-response in zooplankton abundance and microbial decomposition rate of plant material. In the behavioral assays, the locomotion of zooplankton prey D. magna showed a similar non-monotonic response primarily induced by fluoxetine. Its predator C. flavicans, however, showed a significant non-monotonic response governed by both microplastics and fluoxetine. The behavior of the decomposer A. aquaticus significantly decreased at higher fluoxetine concentrations, potentially leading to reduced decomposition rates near the sediment. Our study demonstrates that effects observed upon short-term exposure result in more pronounced ecosystem-level effects following chronic exposure.

Melatonin improves nitric oxide bioavailability in isoproterenol induced myocardial injury.

Isoproterenol administration is associated with cardiac inflammation and decreased NO availability. Melatonin has been reported to have cardioprotective effect. The aim of this study was to investigate the effect of melatonin on NO bioavailability and inflammation in myocardial injury induced by isoproterenol. Isoproterenol was administrated in male Wistar rats for 7 days to induce cardiac injury. The animals were divided into 3 groups: Control, Isoproterenol, Isoproterenol + Melatonin. Animals received melatonin for 7 days. Echocardiographic analysis was performed and the hearts were collected for molecular analysis. Animals that received isoproterenol demonstrated a reduction in left ventricle systolic and diastolic diameter, indicating the presence of concentric hypertrophy. Melatonin was able to attenuate this alteration. Melatonin also improved NO bioavailability and decreased NF-κß, TNFα and IL-1ß expression. In conclusion, melatonin exhibited a cardioprotective effect which was associated with improving NO bioavailability and decreasing the pro-inflammatory proteins.

Mapping the lipidome in mitochondria-associated membranes (MAMs) in an in vitro model of Alzheimer's disease.

The disruption of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) plays a relevant role in Alzheimer's disease (AD). MAMs have been implicated in neuronal dysfunction and death since it is associated with impairment of functions regulated in this subcellular domain, including lipid synthesis and trafficking, mitochondria dysfunction, ER stress-induced unfolded protein response (UPR), apoptosis, and inflammation. Since MAMs play an important role in lipid metabolism, in this study we characterized and investigated the lipidome alterations at MAMs in comparison with other subcellular fractions, namely microsomes and mitochondria, using an in vitro model of AD, namely the mouse neuroblastoma cell line (N2A) over-expressing the APP familial Swedish mutation (APPswe) and the respective control (WT) cells. Phospholipids (PLs) and fatty acids (FAs) were isolated from the different subcellular fractions and analyzed by HILIC-LC-MS/MS and GC-MS, respectively. In this in vitro AD model, we observed a down-regulation in relative abundance of some phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE) species with PUFA and few PC with saturated and long-chain FA. We also found an up-regulation of CL, and antioxidant alkyl acyl PL. Moreover, multivariate analysis indicated that each organelle has a specific lipid profile adaptation in N2A APPswe cells. In the FAs profile, we found an up-regulation of C16:0 in all subcellular fractions, a decrease of C18:0 levels in total fraction (TF) and microsomes fraction, and a down-regulation of 9-C18:1 was also found in mitochondria fraction in the AD model. Together, these results suggest that the over-expression of the familial APP Swedish mutation affects lipid homeostasis in MAMs and other subcellular fractions and supports the important role of lipids in AD physiopathology.

Understanding the differential impacts of two antidepressants on locomotion of freshwater snails (Lymnaea stagnalis).

There is growing evidence of negative impacts of antidepressants on behavior of aquatic non-target organisms. Accurate environmental risk assessment requires an understanding of whether antidepressants with similar modes of action have consistent negative impacts. Here, we tested the effect of acute exposure to two antidepressants, fluoxetine and venlafaxine (0-50 µg/L), on the behavior of non-target organism, i.e., freshwater pond snail, Lymnaea stagnalis. As compounds interact with chemical cues in the aquatic ecosystems, we also tested whether the effects altered in the presence of bile extract containing 5α-cyprinol sulfate (5α-CPS), a characterized kairomone of a natural predator, common carp (Cyprinus carpio). Behavior was studied using automated tracking and analysis of various locomotion parameters of L. stagnalis. Our results suggest that there are differences in the effects on locomotion upon exposure to venlafaxine and fluoxetine. We found strong evidence for a non-monotonic dose response on venlafaxine exposure, whereas fluoxetine only showed weak evidence of altered locomotion for a specific concentration. Combined exposure to compounds and 5α-CPS reduced the intensity of effects observed in the absence of 5α-CPS, possibly due to reduced bioavailability of the compounds. The results highlight the need for acknowledging different mechanisms of action among antidepressants while investigating their environmental risks. In addition, our results underline the importance of reporting non-significant effects and acknowledging individual variation in behavior for environmental risk assessment.

Letters away from the looking glass: Developmental trajectory of mirrored and rotated letter processing within words.

Discrimination of reversible mirrored letters (e.g., d and b) poses a challenge when learning to read as it requires overcoming mirror invariance, an evolutionary-old perceptual tendency of processing mirror images as equivalent. The present study investigated when, in reading development, mirror-image discrimination becomes automatic during visual word recognition. The developmental trajectory of masked priming effects was investigated from 2nd to 6th grade and in adults, by manipulating letter type (nonreversible; reversible) and prime condition (control; identity; mirrored; rotated). Standardized identity priming increased along reading development. Beginning readers showed mirror invariance during reversible and nonreversible letter processing. A mirror cost (slower word recognition in mirrored-letter than identity prime condition) was found by 5th-grade but only for reversible letters. By 6th grade, orthographic processing was no longer captive of mirror invariance. A multiple linear regression showed that letter representations, but not phonological processes or age, were a reliable predictor of the rise of mirror-image discrimination in 2nd-4th-graders. The present results suggest a protracted development of automatic mirror-image discrimination during orthographic processing, contingent upon the quality of abstract letter representations. RESEARCH HIGHLIGHTS: We traced the developmental trajectory of mirrored-letter and rotated-letter priming effects (e.g., ibea and ipea as primes of IDEA) in visual word recognition. Beginning readers (2nd-4th-graders) showed mirror invariance and plane-rotation sensitivity in orthographic processing, thus still being susceptible to the perceptual biases in charge in object recognition. A mirror cost was found in 5th-graders but only for reversible letters; orthographic processing was no longer captive of mirror invariance by 6th-grade. The automation of mirror-image discrimination during orthographic processing depends on the quality of letter representations but not on phonological processes or age.

Impact of mixed microalgal and bacterial species on organic micropollutants removal in photobioreactors under natural light.

Single microalgae species are effective at the removal of various organic micropollutants (OMPs), however increased species diversity might enhance this removal. Sixteen OMPs were added to 2 continuous photobioreactors, one inoculated with Chlorella sorokiniana and the other with a microalgal-bacterial community, for 112 d under natural light. Three media were sequentially used in 3 Periods: I) synthetic sewage (d 0-28), II) 10x diluted anaerobically digested black water (AnBW) (d 28-94) and III) 5x diluted AnBW (d 94-112). Twelve OMPs were removed > 30 %, while 4 were < 10 % removed. Removal efficiencies were similar for 9 OMPs, yet the mixed community showed a 2-3 times higher removal capacity (µg OMP/g dry weight) than C. sorokiniana during Period II pseudo steady state. The removal decreased drastically in Period III due to overgrowth of filamentous green algae. This study shows for the first time how microbial community composition and abundance are key for OMPs removal.

Oral isotretinoin in the treatment of juvenile acne and psychiatric adverse effects - a systematic review.

PURPOSE: Acne vulgaris is a very prevalent dermatological condition, especially among adolescents and young adults up to 25 years old, classifying it as juvenile acne. One of the most effective treatments for severe acne is isotretinoin, a derivative of retinoic acid. Despite its high efficacy, this drug has been linked to several side effects including psychiatric adverse alterations, such as anxiety, depression and even suicide. With this systematic review we aim to determine if it is possible to establish a causal relation between oral isotretinoin in the treatment of juvenile acne and the appearance of psychiatric adverse effects. MATERIALS AND METHODS: We searched two distinct databases, PubMed and Web of Science, and considered the work published between January 2000 and November 2021. RESULTS: Out of the 599 identified articles, we included 19 studies in this systematic review. Globally, the results we found do not support an association between the use of isotretinoin for acne treatment and mental side effects and the safety of this drug appears to be assured. However, the individual characteristics of each adolescent and their environment should be considered; the personal and family history of mental disorders are pointed out as red flags we should look out for when treating these patients. CONCLUSION: Despite this being a highly debated topic, especially among the dermatology community, more studies with larger populations and randomised controlled trials are necessary to increase the strength of the evidence presented.

Impact of wastewater characteristics on the removal of organic micropollutants by Chlorella sorokiniana.

Microalgae-based technologies can be used for the removal of organic micropollutants (OMPs) from different types of wastewater. However, the effect of wastewater characteristics on the removal is still poorly understood. In this study, the removal of sixteen OMPs by Chlorella sorokiniana, cultivated in three types of wastewater (anaerobically digested black water (AnBW), municipal wastewater (MW), and secondary clarified effluent (SCE)), were assessed. During batch operational mode, eleven OMPs were removed from AnBW and MW. When switching from batch to continuous mode (0.8 d HRT), the removal of most OMPs from AnBW and MW decreased, suggesting that a longer retention time enhances the removal of some OMPs. Most OMPs were not removed from SCE since poor nutrient availability limited C. sorokiniana growth. Further correlation analyses between wastewater characteristics, biomass and OMPs removal indicated that the wastewater soluble COD and biomass concentration predominantly affected the removal of OMPs. Lastly, carbon uptake rate had a higher effect on the removal of OMPs than nitrogen and phosphate uptake rate. These data will give an insight on the implementation of microalgae-based technologies for the removal of OMPs in wastewater with varying strengths and nutrient availability.

A Perspective on the Link between Mitochondria-Associated Membranes (MAMs) and Lipid Droplets Metabolism in Neurodegenerative Diseases.

Mitochondria interact with the endoplasmic reticulum (ER) through contacts called mitochondria-associated membranes (MAMs), which control several processes, such as the ER stress response, mitochondrial and ER dynamics, inflammation, apoptosis, and autophagy. MAMs represent an important platform for transport of non-vesicular phospholipids and cholesterol. Therefore, this region is highly enriched in proteins involved in lipid metabolism, including the enzymes that catalyze esterification of cholesterol into cholesteryl esters (CE) and synthesis of triacylglycerols (TAG) from fatty acids (FAs), which are then stored in lipid droplets (LDs). LDs, through contact with other organelles, prevent the toxic consequences of accumulation of unesterified (free) lipids, including lipotoxicity and oxidative stress, and serve as lipid reservoirs that can be used under multiple metabolic and physiological conditions. The LDs break down by autophagy releases of stored lipids for energy production and synthesis of membrane components and other macromolecules. Pathological lipid deposition and autophagy disruption have both been reported to occur in several neurodegenerative diseases, supporting that lipid metabolism alterations are major players in neurodegeneration. In this review, we discuss the current understanding of MAMs structure and function, focusing on their roles in lipid metabolism and the importance of autophagy in LDs metabolism, as well as the changes that occur in neurogenerative diseases.

High resolution functional analysis and community structure of photogranules.

Photogranules are spherical aggregates formed of complex phototrophic ecosystems with potential for "aeration-free" wastewater treatment. Photogranules from a sequencing batch reactor were investigated by fluorescence microscopy, 16S/18S rRNA gene amplicon sequencing, microsensors, and stable- and radioisotope incubations to determine the granules' composition, nutrient distribution, and light, carbon, and nitrogen budgets. The photogranules were biologically and chemically stratified, with filamentous cyanobacteria arranged in discrete layers and forming a scaffold to which other organisms were attached. Oxygen, nitrate, and light gradients were also detectable. Photosynthetic activity and nitrification were both predominantly restricted to the outer 500 µm, but while photosynthesis was relatively insensitive to the oxygen and nutrient (ammonium, phosphate, acetate) concentrations tested, nitrification was highly sensitive. Oxygen was cycled internally, with oxygen produced through photosynthesis rapidly consumed by aerobic respiration and nitrification. Oxygen production and consumption were well balanced. Similarly, nitrogen was cycled through paired nitrification and denitrification, and carbon was exchanged through photosynthesis and respiration. Our findings highlight that photogranules are complete, complex ecosystems with multiple linked nutrient cycles and will aid engineering decisions in photogranular wastewater treatment.

Enhancing phosphorus removal of photogranules by incorporating polyphosphate accumulating organisms.

Photogranules are a novel wastewater treatment technology that can utilize the sun's energy to treat water with lower energy input and have great potential for nutrient recovery applications. They have been proven to efficiently remove nitrogen and carbon but show lower conversion rates for phosphorus compared to established treatment systems, such as aerobic granular sludge. In this study, we successfully introduced polyphosphate accumulating organisms (PAOs) to an established photogranular culture. We operated photobioreactors in sequencing batch mode with six cycles per day and alternating anaerobic (dark) and aerobic (light) phases. We were able to increase phosphorus removal/recovery by 6 times from 5.4 to 30 mg/L/d while maintaining similar nitrogen and carbon removal compared to photogranules without PAOs. To maintain PAOs activity, alternating anaerobic feast and aerobic famine conditions were required. In future applications, where aerobic conditions are dependent on in-situ oxygenation via photosynthesis, the process will rely on sunlight availability. Therefore, we investigated the feasibility of the process under diurnal cycles with a 12-h anaerobic phase during nighttime and six short cycles during the 12 h daytime. The 12-h anaerobic phase had no adverse effect on the PAOs and phototrophs. Due to the extension of one anaerobic phase to 12 h the six aerobic phases were shortened by 47% and consequently decreased the light hours per day. This resulted in a decrease of phototrophs, which reduced nitrogen removal and biomass productivity up to 30%. Finally, we discuss and suggest strategies to apply PAO-enriched photogranules at large-scale.

Cytosolic pH Controls Fungal MAPK Signaling and Pathogenicity.

Mitogen-activated protein kinases (MAPKs) regulate a variety of cellular processes in eukaryotes. In fungal pathogens, conserved MAPK pathways control key virulence functions such as infection-related development, invasive hyphal growth, or cell wall remodeling. Recent findings suggest that ambient pH acts as a key regulator of MAPK-mediated pathogenicity, but the underlying molecular events are unknown. Here, we found that in the fungal pathogen Fusarium oxysporum, pH controls another infection-related process, hyphal chemotropism. Using the ratiometric pH sensor pHluorin we show that fluctuations in cytosolic pH (pHc) induce rapid reprogramming of the three conserved MAPKs in F. oxysporum, and that this response is conserved in the fungal model organism Saccharomyces cerevisiae. Screening of a subset of S. cerevisiae mutants identified the sphingolipid-regulated AGC kinase Ypk1/2 as a key upstream component of pHc-modulated MAPK responses. We further show that acidification of the cytosol in F. oxysporum leads to an increase of the long-chain base (LCB) sphingolipid dihydrosphingosine (dhSph) and that exogenous addition of dhSph activates Mpk1 phosphorylation and chemotropic growth. Our results reveal a pivotal role of pHc in the regulation of MAPK signaling and suggest new ways to target fungal growth and pathogenicity. IMPORTANCE Fungal phytopathogens cause devastating losses in global agriculture. All plant-infecting fungi use conserved MAPK signaling pathways to successfully locate, enter, and colonize their hosts. In addition, many pathogens also manipulate the pH of the host tissue to increase their virulence. Here, we establish a functional link between cytosolic pH (pHc) and MAPK signaling in the control of pathogenicity in the vascular wilt fungal pathogen Fusarium oxysporum. We demonstrate that fluctuations in pHc cause rapid reprogramming of MAPK phosphorylation, which directly impacts key processes required for infection, such as hyphal chemotropism and invasive growth. Targeting pHc homeostasis and MAPK signaling can thus open new ways to combat fungal infection.

N2 -fixation can sustain wastewater treatment performance of photogranules under nitrogen-limiting conditions.

Wastewater characteristics can vary significantly, and in some municipal wastewaters the N:P ratio is as low as 5 resulting in nitrogen-limiting conditions. In this study, the microbial community, function, and morphology of photogranules under nitrogen-replete (N+) and limiting (N-) conditions was assessed in sequencing batch reactors. Photogranules under N- condition were nitrogen deprived 2/3 of a batch cycle duration. Surprisingly, this nitrogen limitation had no adverse effect on biomass productivity. Moreover, phosphorus and chemical oxygen demand removal were similar to their removal under N+ conditions. Although performance was similar, the difference in granule morphology was obvious. While N+ photogranules were dense and structurally confined, N- photogranules showed loose structures with occasional voids. Microbial community analysis revealed high abundance of cyanobacteria capable of N2 -fixation. These were higher at N- (38%) than N+ (29%) treatments, showing that photogranules could adjust and maintain treatment performance and high biomass productivity by means of N2 -fixation.

A randomized controlled trial on the effects of "Global Postural Re-education" versus neck specific exercise on pain, disability, postural control, and neuromuscular features in women with chronic non-specific neck pain.

BACKGROUND: Neck pain is associated with decreased health-related quality of life, decreased work productivity, and increased visits to health care providers. AIM: The aim of this study was to assess the effectiveness of "Global Postural Re-education" (GPR) versus a neck specific exercise (SE) program on neck pain, disability, cervical range of movement, postural stability, and activity of the superficial cervical flexor muscles. DESIGN: A parallel-group and single-blinded clinical trial. SETTING: Community interventions. POPULATION: Fifty women with non-specific chronic neck pain (NSCNP). METHODS: Participants were randomly assigned to one of the two intervention groups (GPR [N.=25] or SE [N.=25]). Both interventions consisted of eight sessions of ~40 minutes duration, performed twice a week, for four weeks. Outcomes included neck pain intensity and disability, cervical range of motion (CROM), postural sway, and activity of the superficial neck flexor muscles during a cranio-cervical flexion test (CCFT). All outcomes were assessed twice before the intervention and immediately following eight treatment sessions over four weeks. RESULTS: Both interventions were equally effective in reducing neck pain (P<0.001, ŋp2=0.770) and disability (P<0.001, ŋp2=0.306), improving neck mobility (P<0.001, 0.385≤ŋp2≤0.623, for all measurements) and decreasing the activity of the superficial cervical flexor muscles (P>0.001). Neither intervention altered postural sway. CONCLUSIONS: Our results revealed that GPR and SE induced significant positive results in all measures apart from postural stability but with no difference between the interventions. CLINICAL REHABILITATION IMPACT: "Global Postural Re-education" (GPR) and neck SE interventions are equally effective in reducing neck pain and disability, and improving neck mobility in women with NSCNP. Overall, this study indicates that GPR and SE interventions can be used to effectively manage patients with NSCNP.

Impact Of The COVID-19 Pandemic on Hospital Admissions and In-Hospital Lethality From Cardiovascular Diseases in Brazil: An Ecological and Time Series Study.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic in Brazil, several government policies have been taken. Herein, we aimed to assess the impact of the COVID-19 pandemic on hospital admissions and in-hospital lethality for cardiovascular diseases (CVD) in Brazil in 2020. An ecological and time-series study on hospitalizations and deaths from CVD in Brazil was conducted from January 2018 to December 2020.The hospital admission rate for CVD reduced by 17.1%, with a significant decreasing trend between January and May 2020 (Annual Percent Change: -8,7%; P-value < 0.001). The in-hospital lethality rate increased from 8.2% in 2018 to 9.3% in 2020. During this period, Brazil totaled 21.8 million days of hospital stay. Indicators of hospital admissions and lethality from CVD in Brazil were impacted by the emergence of the COVID-19 pandemic in different ways in the regions and depending on the nature of the indicator.

Fusarium oxysporum Casein Kinase 1, a Negative Regulator of the Plasma Membrane H+-ATPase Pma1, Is Required for Development and Pathogenicity.

Like many hemibiotrophic plant pathogens, the root-infecting vascular wilt fungus Fusarium oxysporum induces an increase in the pH of the surrounding host tissue. How alkalinization promotes fungal infection is not fully understood, but recent studies point towards the role of cytosolic pH (pHc) and mitogen-activated protein kinase (MAPK) signaling. In fungi, pHc is mainly controlled by the essential plasma membrane H+-ATPase Pma1. Here we created mutants of F. oxysporum lacking casein kinase 1 (Ck1), a known negative regulator of Pma1. We found that the ck1Δ mutants have constitutively high Pma1 activity and exhibit reduced alkalinization of the surrounding medium as well as decreased hyphal growth and conidiation. Importantly, the ck1Δ mutants exhibit defects in hyphal chemotropism towards plant roots and in pathogenicity on tomato plants. Thus, Ck1 is a key regulator of the development and virulence of F. oxysporum.