AMPK regulates phagophore-to-autophagosome maturation.

Autophagy is an important metabolic pathway that can non-selectively recycle cellular material or lead to targeted degradation of protein aggregates or damaged organelles. Autophagosome formation starts with autophagy factors accumulating on lipid vesicles containing ATG9. These phagophores attach to donor membranes, expand via ATG2-mediated lipid transfer, capture cargo, and mature into autophagosomes, ultimately fusing with lysosomes for their degradation. Autophagy can be activated by nutrient stress, for example, by a reduction in the cellular levels of amino acids. In contrast, how autophagy is regulated by low cellular ATP levels via the AMP-activated protein kinase (AMPK), an important therapeutic target, is less clear. Using live-cell imaging and an automated image analysis pipeline, we systematically dissect how nutrient starvation regulates autophagosome biogenesis. We demonstrate that glucose starvation downregulates autophagosome maturation by AMPK-mediated inhibition of phagophore tethering to donor membrane. Our results clarify AMPKs regulatory role in autophagy and highlight its potential as a therapeutic target to reduce autophagy.

Dysphagia and stenosis secondary to intramural esophageal pseudodiverticulosis.

We present the case of a patient with smoking, alcoholism, cirrhosis and HIV who was endoscopically diagnosed with esophageal candidiasis due to an episode of dysphagia. After treatment with antifungals and PPIs, the patient remained asymptomatic for almost 3 years. He presented an event of food impaction that was resolved by an upper endoscopy in which an esophageal stenosis and multiple esophageal pseudodiverticulosis were visualized. The biopsies only showed chronic nonspecific esophagitis. The stenosis was dilated with a balloon and PPIs were continued, with good response. Esophageal intramural pseudodiverticulosis is rare and can lead to motor disorders and strictures. It has a doubtful association with HIV and a clearer relationship with alcoholism, smoking, diabetes, reflux and candidiasis. The endoscopic diagnosis can be difficult so in order to make an accurate diagnosis is necessary an esophagram or CT. Treatment is based on controlling risk factors and dilating stenosis. The prognosis is usually favorable.

Preparing healthcare facilities in sub-Saharan Africa for future outbreaks: insights from a multi-country digital self-assessment of COVID-19 preparedness.

BACKGROUND: Despite previous experience with epidemics, African healthcare systems were inadequately prepared and substantially impacted by the coronavirus disease 2019 (COVID-19) pandemic. Limited information about the level of COVID-19 preparedness of healthcare facilities in Africa hampers policy decision-making to fight future outbreaks in the region, while maintaining essential healthcare services running. METHODS: Between May-November 2020, we performed a survey study with SafeCare4Covid - a free digital self-assessment application - to evaluate the COVID-19 preparedness of healthcare facilities in Africa following World Health Organization guidelines. The tool assessed (i) COVID-19-related capabilities with 31 questions; and (ii) availability of essential medical supplies with a 23-supplies checklist. Tailored quality improvement plans were provided after assessments. Information about facilities' location, type, and ownership was also collected. RESULTS: Four hundred seventy-one facilities in 11 African countries completed the capability assessment; 412 also completed the supplies checklist. The average capability score on a scale of 0-100 (n=471) was 58.0 (interquartile range 40.0-76.0), and the average supplies score (n=412) was 61.6 (39.0-83.0). Both scores were significantly lower in rural (capability score, mean 53.6 [95%CI:50.3-57.0]/supplies score, 59.1 [55.5-62.8]) versus urban facilities (capability score, 65.2 [61.7-68.7]/supplies score, 70.7 [67.2-74.1]) (P<0.0001 for both comparisons). Likewise, lower scores were found for public versus private clinics, and for primary healthcare centres versus hospitals. Guidelines for triage and isolation, clinical management of COVID-19, staff mental support, and contact tracing forms were largely missing. Handwashing stations were partially equipped in 33% of facilities. The most missing medical supply was COVID-19 specimen collection material (71%), while 43% of facilities did not have N95/FFP2 respirators and 19% lacked medical masks. CONCLUSIONS: A large proportion of public and private African facilities providing basic healthcare in rural areas, lacked fundamental COVID-19-related capabilities and life-saving personal protective equipment. Decentralization of epidemic preparedness efforts in these settings is warranted to protect healthcare workers and patients alike in future epidemics. Digital tools are of great value to timely measure and improve epidemic preparedness of healthcare facilities, inform decision-making, create a more stakeholder-broad approach and increase health-system resilience for future disease outbreaks.

Periostin in the relation between periodontal disease and atherosclerotic coronary artery disease: A pilot randomized clinical study.

OBJECTIVE: The aim of this study was to analyze the effects of periodontal treatment on markers of atherosclerotic coronary artery disease and circulating levels of periostin. BACKGROUND: Periostin is necessary for periodontal stability, but it is highly present in atherosclerotic plaques. Treatment of periodontal disease, with low levels of local periostin, is thought to reduce systemic levels of periostin. Thus, this may contribute to cardiovascular health. METHODS: A pilot randomized controlled clinical trial was designed to include patients with severe periodontal disease and history of atherosclerotic coronary artery disease. Samples of gingival crevicular fluid (GCF) and serum were collected before and after periodontal treatment by periodontal surgery or non-surgical therapy. The levels of several markers of inflammation and cardiovascular damage were evaluated including CRP, IFN-γ, IL-1ß, IL-10, MIP-1α, periostin, and TNF-α in GCF and CRP, Fibrinogen, IFN-γ, IL-1ß, IL-6, IL-10, L-Selectin, MIP-1α, Periostin, TNF-α, and vWF in serum. RESULTS: A total of 22 patients with an average of 56 years old were recruited for participating in this study. Twenty of them were male. Most of them (82%) had suffered an acute myocardial event and underwent surgery for placing 1, 2, or 3 stents in the coronary arteries more than 6 months ago but less than 1 year. The treatment of periodontal disease resulted in an overall improvement of all periodontal parameters. Regarding the evaluation of GCF and serum, a significant increase of periostin in the GCF was observed after periodontal surgery. In contrast, although other markers in GCF and serum improved, no significant correlations were found. CONCLUSION: Treatment of periodontal disease through periodontal surgery induces a local and transient increase in the levels of periostin in the gingival crevicular fluid. The effects on systemic markers of inflammation and cardiovascular function have not been confirmed.

Colocación de prótesis esofágica para el fracaso del tratamiento endoscópico / Esophageal stent placement for endoscopic treatment failure

Up until approximately 10 years ago, the treatment for acute refractory esophageal variceal bleeding was balloon tamponading. Esophageal fully covered self-expanding stents are considered as effective as balloons and also much safer. They are kept in situ for longer periods, what eases the access to more definitive treatments with a low complication rate. We present 6 cases of patients with cirrhosis and massive bleeding due to esophageal varices refractory to conventional treatment, successfully treated with an esophageal fully covered self-expanding stent. There were no major complications, achieving an effective bleeding control in all cases.(AU)

Assessment of Knowledge and Attitudes Over Time in Postacute COVID-19 Environments: Protocol for an Epidemiological Study.

BACKGROUND: Globally, COVID-19 is in transition from the acute pandemic phase into a postacute phase, and special attention should be paid at this time to COVID-19 control strategies. Understanding public knowledge and attitudes plays a pivotal role in controlling COVID-19's spread and provides information about the public's adherence to preventive and control measures. OBJECTIVE: This study protocol describes the planning and management of a survey to investigate the persistent or changing trends in knowledge and attitudes regarding COVID-19, vaccination, and nonpharmaceutical preventive measures among COVID-19 cases' household contacts aged 18 years and older, after the acute phase of the pandemic in Catalonia and Navarre in Spain. The secondary objectives include investigating the rate of secondary transmission in households, taking into account the demographic characteristics, clinical manifestations, and preventive measures toward COVID-19. METHODS: A telephone questionnaire was designed to assess the changing trends in knowledge, preventive measures, and attitudes toward COVID-19 in 3 rounds (after identification as a household contact, 3 months later, and 6 months later). The questionnaire was developed following an extensive literature review and through discussions with a panel of experts who designed and assessed the validity of the questionnaire in terms of relevance, consistency, completeness, and clarity. The questionnaire consists of the following 7 sections: social and demographic characteristics (ie, gender, age, educational level, and workplace), comorbidities and risk factors (according to the recommendations from the COVID-19 vaccination strategy), epidemiological data (ie, exposure time, relationship with index cases, and frequency of use of nonpharmaceutical preventive measures), COVID-19 vaccination status (ie, the number and date of doses received), knowledge and attitudes toward COVID-19 (assessed using a 5-point Likert scale-totally agree, agree, neither agree nor disagree, disagree, and totally disagree), and sources of information (including traditional mass media, social media, and official sources). RESULTS: A pilot study was performed in May 2022 to evaluate the questionnaire with 22 household contacts. Preliminary findings indicated that the questionnaire was feasible and acceptable in the general population. The average response time was 15 minutes, with greater variations in responses by older participants. After the pilot study, recruitment of participants began and is expected to be completed at the end of the year 2023, after which the final results will be available in 2024. CONCLUSIONS: Despite the low transmission levels of SARS-CoV-2 and the relaxation of containment measures, the implementation of the survey during the postacute phase will provide valuable insight to assist public health decision-making and control the transmission of SARS-CoV-2 and other respiratory viruses, thereby attenuating the negative effects of COVID-19 at individual and population level. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52114.

[An evaluation of teacher training to promote healthy and equitable relationships: transforming or reproducing?] / Evaluación de la formación a profesorado para promover relaciones saludables y equitativas: ¿transformar o reproducir?

OBJECTIVE: To evaluate the impact of the training on teacher capacity to implement Posem el Focus, a socio-educational intervention adapted from Lights4Violence to prevent the gender-based violence during adolescence. METHOD: Evaluation study of a training using qualitative methodology in Terrassa, 2019-2021. The socio-constructionist perspective was used to understand the impact of teacher training and its translation into educational practice. A purposive sampling of teachers (n=32) was carried out. A descriptive-interpretative analysis of the discourses was carried out based on the written productions of the participants in the training and their answers to some open questions. An explanatory theoretical framework was developed. RESULTS: Teachers reported acquiring concepts, developing new skills and modifying some attitudes. Teachers stated theoretical understanding of the sex-gender system, intersectionality and explicit and implicit violence. However, they reproduced gender stereotypes, did not understand the inclusive approach and pointed out not identifying implicit violence. Teachers perceived the training as useful and felt empowered to implement the intervention. No differences were identified in discursive production with respect to gender or age. CONCLUSIONS: Teacher training ensures minimum knowledge and facilitates the acquisition of some skills, although it does not achieve in-depth changes in attitudes. It is concluded that the training enables teachers to implement Posem el Focus, although it is recommended that it be reformulated.

Corrigendum: Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes.

[This corrects the article DOI: 10.3389/fmicb.2023.1149145.].

AMPK Regulates Phagophore-to-Autophagosome Maturation.

Autophagy is an important metabolic pathway that can non-selectively recycle cellular material or lead to targeted degradation of protein aggregates or damaged organelles. Autophagosome formation starts with autophagy factors accumulating on lipid vesicles containing ATG9. These phagophores attach to donor membranes, expand via ATG2-mediated lipid transfer, capture cargo, and mature into autophagosomes, ultimately fusing with lysosomes for their degradation. Autophagy can be activated by nutrient stress, for example by a reduction in the cellular levels of amino acids. In contrast, how autophagy is regulated by low cellular ATP levels via the AMP-activated protein kinase (AMPK), an important therapeutic target, is less clear. Using live-cell imaging and an automated image analysis pipeline, we systematically dissect how nutrient starvation regulates autophagosome biogenesis. We demonstrate that glucose starvation downregulates autophagosome maturation by AMPK mediated inhibition of phagophores tethering to donor membranes. Our results clarify AMPK's regulatory role in autophagy and highlight its potential as a therapeutic target to reduce autophagy.

[Germina: tool for automatic detection of clusters of COVID-19 cases]. / Germina: herramienta para la detección automática de agrupaciones de casos de COVID-19.

The COVID-19 pandemic showed that epidemiological surveillance was under-resourced to respond to increases in cases and outbreaks. The high community transmissibility among the school population in the city of Barcelona at the beginning of the sixth wave strained the local COVID-19 surveillance unit. Using SCRUM methodology, Germina was developed and implemented as a software tool capable of capturing, harmonizing, integrating, storing, analysing and visualizing data from multiple information sources on a daily basis. Germina identifies clusters of three or more school cases and calculates epidemiological indicators. The implementation of Germina facilitated the epidemiological response to the sixth wave of COVID-19 in the school setting in the city of Barcelona. This tool is transferable to other exposure settings and communicable diseases. The use of automated informatics tools such, as Germina, improves epidemiological surveillance systems and supports evidence-based decision making.

Abordaje robótico de la exenteración pélvica masculina. Sistematización de la técnica / Robotic pelvic exenteration in males: Systematization of the technique

La exenteración pélvica masculina es un procedimiento complejo con elevada morbilidad. En casos muy seleccionados, el abordaje robótico puede facilitar la disección y reducir la morbilidad gracias a la mejor visión y versatilidad de movimientos. Describimos la técnica de exenteración pélvica robótica sistematizada con DaVinci Xi y sus variantes en varones, tras haber intervenido tres casos en nuestro Centro. Describimos la colocación de trocares, material necesario, localización de minilaparotomía y secuencia de los procedimientos a realizar paso a paso. Distinguimos tres supuestos: exenteración pélvica total con amputación de recto, colostomía y urostomía; exenteración pélvica con preservación de esfínter, anastomosis colo-rectal/anal y urostomía; exenteración pélvica con amputación de recto, colostomía y reconstrucción de tracto urinario. (AU)

Male pelvic exenteration is a challenging procedure with high morbidity. In very selected cases robotic approach could make dissection easier and decrease morbidity due to a better view and higher range of movements. In this paper we describe port placement, instruments, minilaparotomy location and sequence of procedures step by step. We differentiate three situations: total pelvic exenteration with abdominoperineal resection, colostomy and urostomy; pelvic exenteration with colo-rectal/anal anastomosis and urostomy; pelvic exenteration with abdominoperineal resection, colostomy and urinary tract reconstruction. (AU)

Reduced incidence of respiratory, gastrointestinal and malaria infections among children during the COVID-19 pandemic in Western Kenya: An analysis of facility-based and weekly diaries data.

Background: Epidemics can cause significant disruptions of essential health care services. This was evident in West-Africa during the 2014-2016 Ebola outbreak, raising concerns that COVID-19 would have similar devastating consequences for the continent. Indeed, official facility-based records show a reduction in health care visits after the onset of COVID-19 in Kenya. Our question is whether this observed reduction was caused by lower access to health care or by reduced incidence of communicable diseases resulting from reduced mobility and social contacts. Methods: We analysed monthly facility-based data from 2018 to 2020, and weekly health diaries data digitally collected by trained fieldworkers between February and November 2020 from 342 households, including 1974 individuals, in Kisumu and Kakamega Counties, Kenya. Diaries data was collected as part of an ongoing longitudinal study of a digital health insurance scheme (Kakamega), and universal health coverage implementation (Kisumu). We assessed the weekly incidence of self-reported medical symptoms, formal and informal health-seeking behaviour, and foregone care in the diaries and compared it with facility-based records. Linear probability regressions with household fixed-effects were performed to compare the weekly incidence of health outcomes before and after COVID-19. Results: Facility-based data showed a decrease in health care utilization for respiratory infections, enteric illnesses, and malaria, after start of COVID-19 measures in Kenya in March 2020. The weekly diaries confirmed this decrease in respiratory and enteric symptoms, and malaria / fever, mainly in the paediatric population. In terms of health care seeking behaviour, our diaries data find a temporary shift in consultations from health care centres to pharmacists / chemists / medicine vendors for a few weeks during the pandemic, but no increase in foregone care. According to the diaries, for adults the incidence of communicable diseases/symptoms rebounded after COVID-19 mobility restrictions were lifted, while for children the effects persisted. Conclusions: COVID-19-related containment measures in Western Kenya were accompanied by a decline in respiratory infections, enteric illnesses, and malaria / fever mainly in children. Data from a population-based survey and facility-based records aligned regarding this finding despite the temporary shift to non-facility-based consultations and confirmed that the drop in utilization of health care services was not due to decreased accessibility, but rather to a lower incidence of these infections.

Socioeconomic inequalities in COVID-19 incidence during the first six waves in Barcelona.

BACKGROUND: The emergence of SARS-CoV-2 affected urban areas. In Barcelona, six waves of COVID-19 hit the city between March 2020 and March 2022. Inequalities in the incidence of COVID-19 have been described. However, no studies have examined the daily trends of socioeconomic inequalities and how they changed during the different phases of the pandemic. The aim of this study is to analyse the dynamic socioeconomic inequalities in the incidence of COVID-19 during the six waves in Barcelona. METHODS: We examined the proportion of daily cases observed in the census tracts in the lower income tercile compared with the proportion of daily cases observed in the sum of the lower and higher income terciles. Daily differences in these proportions were assessed as a function of the epidemic waves, sex, age group, daily incidence and daily change in the incidence. A logistic regression model with an autoregressive term was used for statistical analysis. RESULTS: A time-dynamic effect was found for socioeconomic inequalities in the incidence of COVID-19. In fact, belonging to a lower-income area changed from being a risk factor (Waves 1, 2, 4 and 5) to being a protective factor in the sixth wave of the pandemic. Age also had a significant effect on incidence, which also changed over the different waves of the pandemic. Finally, the lower-income areas showed a comparatively lower incidence during the ascending phase of the epidemic waves. CONCLUSION: Socioeconomic inequalities in COVID-19 changed by wave, age group and wave phase.

Robotic pelvic exenteration in males: systematization of the technique.

Male pelvic exenteration is a challenging procedure with high morbidity. In very selected cases, the robotic approach could make dissection easier and decrease morbidity due to the better vision provided and higher range of movements. In this paper, we describe port placement, instruments, minilaparotomy location, and the stepwise sequence of these procedures. We address 3 different situations: total pelvic exenteration with abdominoperineal resection, colostomy and urostomy; pelvic exenteration with colorectal/anal anastomosis and urostomy; and pelvic exenteration with abdominoperineal resection, colostomy and urinary tract reconstruction.

Community outbreak of COVID-19 among people who use drugs attending a harm reduction centre in Barcelona, Spain.

BACKGROUND: The COVID-19 pandemic particularly affected the health of vulnerable population, such as people who use drugs. Due to compromised baseline health status, certain drug uses and settings and socioeconomic deprivation related to poverty and homelessness, drug users faced higher risk of COVID-19 infection. They had difficulty in adhering to the public health measures (i.e. physical distancing, hand hygiene and mask use). Also, the struggle to implement non-pharmaceutical actions (i.e. test-trace-isolate-quarantine strategy) among SARS-COV-2-infected drug users and their close contacts challenged the public health response. Therefore, this study aimed to describe a community COVID-19 outbreak and its approach among drug users of a harm reduction programme in an outpatient drug treatment centre in Barcelona, Spain. METHODS: We conducted an observational descriptive study of an outbreak of COVID-19 among people who use drugs attending the harm reduction programme of an outpatient drug treatment centre in the city of Barcelona, between July and October 2021 (n = 440). A passive search for cases was carried out with rapid antigens tests targeting symptomatic users who attended the facilities. RESULTS: Nineteen positive COVID-19 cases were identified among symptomatic drug users, between July and October 2021, with an attack rate of 4.3%. Specific measures were taken to control the outbreak, such as offering accommodation to self-isolate in a low-threshold residential resource to homeless drug users who tested positive and intensifying the vaccination strategy. The management of the outbreak was carried out in close collaboration between the outpatient centre and the main public health stakeholders in the city of Barcelona. CONCLUSIONS: This study shows the complexity of managing and investigating COVID-19 outbreaks in vulnerable population groups. Epidemiological control measures, such as the test-trace-isolate-quarantine strategy, were challenging to implement due to technology-related barriers and socioeconomic vulnerabilities, especially homelessness. Community-based interventions, cooperation among stakeholders and housing-related policies were helpful in tackling outbreaks among people who use drugs. When addressing vulnerable and hidden populations, the perspective of inequalities should be included in epidemiological surveillance and outbreak control strategies.

TCAB1 prevents nucleolar accumulation of the telomerase RNA to facilitate telomerase assembly.

Localization of a variety of RNAs to non-membrane-bound cellular compartments such as nucleoli and Cajal bodies is critical for their stability and function. The molecular mechanisms that underly the recruitment and exclusion of RNAs from these phase-separated organelles is incompletely understood. Telomerase is a ribonucleoprotein composed of the reverse transcriptase protein telomerase reverse transcriptase (TERT), the telomerase RNA (TR), and several auxiliary proteins, including TCAB1. Here we show that in the absence of TCAB1, a large fraction of TR is tightly bound to the nucleolus, while TERT is largely excluded from the nucleolus, reducing telomerase assembly. This suggests that nuclear compartmentalization by the non-membrane-bound nucleolus counteracts telomerase assembly, and TCAB1 is required to retain TR in the nucleoplasm. Our work provides insight into the mechanism and functional consequences of RNA recruitment to organelles formed by phase separation and demonstrates that TCAB1 plays an important role in telomerase assembly.

Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes.

Acanthamoeba species, Naegleria fowleri, and Balamuthia mandrillaris are opportunistic pathogens that cause a range of brain, skin, eye, and disseminated diseases in humans and animals. These pathogenic free-living amoebae (pFLA) are commonly misdiagnosed and have sub-optimal treatment regimens which contribute to the extremely high mortality rates (>90%) when they infect the central nervous system. To address the unmet medical need for effective therapeutics, we screened kinase inhibitor chemotypes against three pFLA using phenotypic drug assays involving CellTiter-Glo 2.0. Herein, we report the activity of the compounds against the trophozoite stage of each of the three amoebae, ranging from nanomolar to low micromolar potency. The most potent compounds that were identified from this screening effort were: 2d (A. castellanii EC50: 0.92 ± 0.3 µM; and N. fowleri EC50: 0.43 ± 0.13 µM), 1c and 2b (N. fowleri EC50s: <0.63 µM, and 0.3 ± 0.21 µM), and 4b and 7b (B. mandrillaris EC50s: 1.0 ± 0.12 µM, and 1.4 ± 0.17 µM, respectively). With several of these pharmacophores already possessing blood-brain barrier (BBB) permeability properties, or are predicted to penetrate the BBB, these hits present novel starting points for optimization as future treatments for pFLA-caused diseases.

In Vivo Analysis of Heterogeneous Extracellular Vesicles Using a Red-Shifted Bioluminescence Resonance Energy Transfer Reporter Protein.

Current methods for characterizing the biodistribution of extracellular vesicles (EVs) are not sensitive enough to track EVs in vivo, despite significant advances over the past decade. Commonly used lipophilic fluorescent dyes are convenient, but lack specificity and yield inaccurate spatiotemporal images in the long-term tracking of EVs. In contrast, protein-based fluorescent or bioluminescent EV reporters have more accurately revealed their distribution in cells and mouse models. Here, we describe a red-shifted bioluminescence resonance energy transfer (BRET) EV reporter, PalmReNL, to analyze the trafficking of small EVs (<200 nm; sEVs) and medium/large EVs (>200 nm; m/lEVs) in mice. Its advantages are that (i) background signals in bioluminescence imaging (BLI) are negligible and (ii) the photons PalmReNL emits have spectral wavelengths longer than 600 nm and can more efficiently penetrate tissues than reporters emitting shorter wavelength light.

Quantitative analysis of autophagy reveals the role of ATG9 and ATG2 in autophagosome formation.

Autophagy is a catabolic pathway required for the recycling of cytoplasmic materials. To define the mechanisms underlying autophagy it is critical to quantitatively characterize the dynamic behavior of autophagy factors in living cells. Using a panel of cell lines expressing HaloTagged autophagy factors from their endogenous loci, we analyzed the abundance, single-molecule dynamics, and autophagosome association kinetics of autophagy proteins involved in autophagosome biogenesis. We demonstrate that autophagosome formation is inefficient and ATG2-mediated tethering to donor membranes is a key commitment step in autophagosome formation. Furthermore, our observations support the model that phagophores are initiated by the accumulation of autophagy factors on mobile ATG9 vesicles, and that the ULK1 complex and PI3-kinase form a positive feedback loop required for autophagosome formation. Finally, we demonstrate that the duration of autophagosome biogenesis is ∼110 s. In total, our work provides quantitative insight into autophagosome biogenesis and establishes an experimental framework to analyze autophagy in human cells.

Role of the RNA-binding protein ZC3H41 in the regulation of ribosomal protein messenger RNAs in trypanosomes.

BACKGROUND: Trypanosomes are single-celled eukaryotes that rely heavily on post-transcriptional mechanisms to regulate gene expression. RNA-binding proteins play essential roles in regulating the fate, abundance and translation of messenger RNAs (mRNAs). Among these, zinc finger proteins of the cysteine3histidine (CCCH) class have been shown to be key players in cellular processes as diverse as differentiation, regulation of the cell cycle and translation. ZC3H41 is an essential zinc finger protein that has been described as a component of spliced leader RNA granules and nutritional stress granules, but its role in RNA metabolism is unknown. METHODS: Cell cycle analysis in ZC3H41- and Z41AP-depleted cells was carried out using 4',6-diamidino-2-phenylindole staining, microscopic examination and flow cytometry. The identification of ZC3H41 protein partners was done using tandem affinity purification and mass spectrometry. Next-generation sequencing was used to evaluate the effect of ZC3H41 depletion on the transcriptome of procyclic Trypanosoma brucei cells, and also to identify the cohort of mRNAs associated with the ZC3H41/Z41AP complex. Levels of 5S ribosomal RNA (rRNA) species in ZC3H41- and Z41AP-depleted cells were assessed by quantitative reverse transcription-polymerase chain reaction. Surface sensing of translation assays were used to monitor global translation. RESULTS: We showed that depletion of the zinc finger protein ZC3H41 resulted in marked cell cycle defects and abnormal cell morphologies. ZC3H41 was found associated with an essential protein, which we named Z41AP, forming a stable heterodimer, and also with proteins of the poly(A)-binding protein 1 complex. The identification of mRNAs associated with the ZC3H41/Z41AP complex revealed that it is primarily composed of ribosomal protein mRNAs, and that binding to target transcripts is diminished upon nutritional stress. In addition, we observed that mRNAs encoding several proteins involved in the maturation of 5S rRNA are also associated with the ZC3H41/Z41AP complex. Finally, we showed that depletion of either ZC3H41 or Z41AP led to the accumulation of 5S rRNA precursors and a decrease of protein translation. CONCLUSIONS: We propose that ZC3H41 and Z41AP play important roles in controlling the fate of ribosomal components in response to environmental cues.