Letter to the Editor
Regulation of secondary metabolism by calmodulin signaling in filamentous fungi
Regulación del metabolismo secundario mediante la señalización con calmodulina en hongos filamentosos
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Fuster-Escrivá, Mercedes Chanzá-Aviñó, Concepción Gimeno-Cardona" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Begoña" "apellidos" => "Fuster-Escrivá" ] 1 => array:2 [ "nombre" => "Mercedes" "apellidos" => "Chanzá-Aviñó" ] 2 => array:1 [ "apellidos" => "Concepción Gimeno-Cardona" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1130140619300361?idApp=UINPBA00004N" "url" => "/11301406/0000003600000003/v1_201911190704/S1130140619300361/v1_201911190704/es/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Regulation of secondary metabolism by calmodulin signaling in filamentous fungi" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "167" "paginaFinal" => "168" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Mi-Hee Kim, Young-Ji Choi, Bora Kwon, Young-Moo Choo, Kang-Yeol Yu, Jiyoung Kim" "autores" => array:6 [ 0 => array:3 [ "nombre" => "Mi-Hee" "apellidos" => "Kim" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Young-Ji" "apellidos" => "Choi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Bora" "apellidos" => "Kwon" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Young-Moo" "apellidos" => "Choo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Kang-Yeol" "apellidos" => "Yu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:4 [ "nombre" => "Jiyoung" "apellidos" => "Kim" "email" => array:1 [ 0 => "jiyoungk1972@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Jeonju AgroBio-Materials Institute, Jeonju-si, Republic of Korea" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "National Marine Biodiversity Institute of Korea, Seocheon-gun, Republic of Korea" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Regulación del metabolismo secundario mediante la señalización con calmodulina en hongos filamentosos" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1196 "Ancho" => 2465 "Tamanyo" => 143918 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Regulation of secondary metabolism by calmodulin signaling in <span class="elsevierStyleItalic">B. bassiana</span>. (A) CaM-binding domains of BbPAL and BbKIVR in <span class="elsevierStyleItalic">B. bassiana</span>. (B) BbPAL contains a 1–5–8–14 motif in the C-terminal region for CaM-binding and BbKIVR has a 1–12 motif in the N-terminal region. (C) Suppression of phenylpropanoid pathway and beauvericin biosynthesis by calmodulin in <span class="elsevierStyleItalic">B. bassiana</span>.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Calmodulin (CaM) is a ubiquitous Ca<span class="elsevierStyleSup">2+</span>-binding receptor that modulates diverse target proteins and biological processes in all eukaryotes.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,6,7</span></a> CaM-binding proteins have been extensively studied in yeasts, plants and animals, but little is known regarding CaM target proteins in the filamentous fungi.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,6,7</span></a> Recently, our studies have shown that CaM plays an important role in the secondary metabolism of <span class="elsevierStyleItalic">Beauveria bassiana</span> (a filamentous fungus) through the regulation of <span class="elsevierStyleItalic">Bb</span>KIVR and <span class="elsevierStyleItalic">Bb</span>PAL.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3,4</span></a> In this way, the isolation and characterization of CaM-binding proteins involved in the fungal secondary metabolism will provide novel aspects of the CaM-mediated signaling pathway unique to filamentous fungi.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Binding of CaM to the target protein modulates structural changes in both the CaM and the target protein. In general, CaM binds to calcium ions with high affinity (<span class="elsevierStyleItalic">K</span><span class="elsevierStyleInf">d</span> 10<span class="elsevierStyleSup">−5</span>–10<span class="elsevierStyleSup">−6</span><span class="elsevierStyleHsp" style=""></span>M), particularly by environmental stimuli.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,6,7</span></a> CaM can affect a variety of biological activities through the direct binding of many cellular proteins in Ca<span class="elsevierStyleSup">2+</span>-dependent manner. As the intracellular Ca<span class="elsevierStyleSup">2+</span> concentration rises to 10<span class="elsevierStyleSup">−5</span><span class="elsevierStyleHsp" style=""></span>M, the four Ca<span class="elsevierStyleSup">2+</span> ions bind to CaM and initiate various types of downstream signaling pathways. CaM has four EF-hand motifs that change shape during calcium ion binding.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,6,7</span></a> In the absence of calcium, the α-helix of EF-hand motif of CaM is nearly parallel to each other.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,6,7</span></a> In this case, CaM also regulates many biological activities through the direct binding with target proteins in a Ca<span class="elsevierStyleSup">2+</span>-independent manner.</p><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">B. bassiana</span> acts as a parasite of various arthropods, causing white muscardine disease. Thus, it belongs to the group of insect pathogens. Beauvericin is a cyclooligomer depsipeptide with many cellular effects.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> Non-ribosomal peptides, such as beauvericin, belong to a broad family of biologically active natural products. Hydroxyisovalerate (Hiv) is a common 2-hydroxycarboxylic acid constituent of depsipeptides such as beauvericin. In <span class="elsevierStyleItalic">B. bassiana</span>, Hiv is formed by the specific reduction of 2-ketoisovalerate (Kiv) by 2-ketoisovalerate reductase (KIVR). We found that <span class="elsevierStyleItalic">Bb</span>KIVR interacts with CaM <span class="elsevierStyleItalic">in vitro</span> and <span class="elsevierStyleItalic">in vivo</span>.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> The functional role of CaM-binding to <span class="elsevierStyleItalic">Bb</span>KIVR is to suppress <span class="elsevierStyleItalic">Bb</span>KIVR activity. Environmental stimuli, such as light and salt stress, inhibit <span class="elsevierStyleItalic">Bb</span>KIVR activity. This negative effect on <span class="elsevierStyleItalic">Bb</span>KIVR activity caused by light and salt stress is partially reversed by CaM inhibitors (such as W-5 and W-7), suggesting that inhibition of <span class="elsevierStyleItalic">Bb</span>KIVR by stress is mediated by the stimulation of CaM. Thus, the KIVR-mediated beauvericin biosynthesis is highly regulated by molecular crosstalk between beauvericin biosynthesis and CaM signaling to respond to light or salt stress.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> Beauvericin is a fungal product with a variety of biological activities such as insecticidal, antimicrobial, antiviral and cytotoxic activities. These useful bioactive activities make beauvericin a potential target for agricultural and pharmaceutical applications. Through the mutation of the CaM binding motif of <span class="elsevierStyleItalic">Bb</span>KIVR, using an <span class="elsevierStyleItalic">in vitro</span> mutagenesis method, it will be possible to develop a <span class="elsevierStyleItalic">B. bassiana</span> strain that increases the biosynthesis of beauvericin by preventing the inhibitory effect of CaM. Fungi produce many secondary metabolites that play an important role in a variety of cellular and molecular responses. Many secondary metabolites are being used for agricultural, pharmaceutical and industrial applications. Fungi directly synthesize phenylalanine in the shikimic acid pathway. Phenylalanine is either used directly for protein synthesis or metabolized through the phenylpropanoid pathway. The phenylpropanoid pathway is an essential biosynthetic pathway for the production of a variety of secondary metabolites.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> Phenylalanine ammonia lyase (PAL), the first key enzyme in the phenylpropanoid pathway, catalyzes the deamination of phenylalanine to cinnamic acid.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> There is much information about the structure, expression and function of PAL in plants, but the biological function of fungal PAL has not been established.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> Significantly, our study has showed that <span class="elsevierStyleItalic">Bb</span>PAL interacts with CaM <span class="elsevierStyleItalic">in vitro</span> and <span class="elsevierStyleItalic">in vivo</span>, indicating that <span class="elsevierStyleItalic">Bb</span>PAL is a novel CaM binding protein in <span class="elsevierStyleItalic">B. bassiana</span>.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> The functional role of CaM in <span class="elsevierStyleItalic">Bb</span>PAL action is to inhibit <span class="elsevierStyleItalic">Bb</span>PAL activity. High-performance liquid chromatography shows that phenylalanine is reduced and cinnamic acid is increased in response to the CaM inhibitor W-7.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> Darkness inhibits <span class="elsevierStyleItalic">Bb</span>PAL activity compared to light. Heat or cold also inhibit <span class="elsevierStyleItalic">Bb</span>PAL activity. This negative effect of <span class="elsevierStyleItalic">Bb</span>PAL activity is partially reversed by W-7 treatment, suggesting that the stimulation of CaM leads to this inhibitory mechanism. In fact, this study presents a new discovery of the PAL-mediated phenylpropanoid pathway in that <span class="elsevierStyleItalic">Bb</span>PAL responds rapidly to environmental stress by regulating crosstalk between the phenylpropanoid pathway and CaM signaling.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> Through the mutation of the CaM binding motif of <span class="elsevierStyleItalic">Bb</span>PAL (that implies preventing the inhibitory effect by CaM), it would be possible to produce a <span class="elsevierStyleItalic">B. bassiana</span> strain with an increased production of valuable secondary metabolites (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">To date, little research has been done on identifying novel CaM target proteins in filamentous fungi. Recently, we have identified and characterized some CaM target proteins in <span class="elsevierStyleItalic">B. bassiana</span> involved in fungal secondary metabolism.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3,4</span></a> However, the information of CaM-mediated signal transduction pathway is still weak in filamentous fungi compared to other eukaryotes. In the near future, it would be of great help to establish an overall CaM-mediated signaling mechanism in the filamentous fungi.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors declare that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => array:2 [ "identificador" => "xack434617" "titulo" => "Acknowledgements" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1196 "Ancho" => 2465 "Tamanyo" => 143918 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Regulation of secondary metabolism by calmodulin signaling in <span class="elsevierStyleItalic">B. bassiana</span>. (A) CaM-binding domains of BbPAL and BbKIVR in <span class="elsevierStyleItalic">B. bassiana</span>. (B) BbPAL contains a 1–5–8–14 motif in the C-terminal region for CaM-binding and BbKIVR has a 1–12 motif in the N-terminal region. (C) Suppression of phenylpropanoid pathway and beauvericin biosynthesis by calmodulin in <span class="elsevierStyleItalic">B. bassiana</span>.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic analysis of calmodulin and its targets in <span class="elsevierStyleItalic">Saccharomyces cerevisiae</span>" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.S. Cyert" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1146/annurev.genet.35.102401.091302" "Revista" => array:6 [ "tituloSerie" => "Annu Rev Genet" "fecha" => "2001" "volumen" => "35" "paginaInicial" => "647" "paginaFinal" => "672" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11700296" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0045" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fungal and plant phenylalanine ammonia-lyase" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.W. Hyun" 1 => "Y.H. Yun" 2 => "J.Y. Kim" 3 => "S.H. Kim" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5941/MYCO.2011.39.4.257" "Revista" => array:6 [ "tituloSerie" => "Mycobiology" "fecha" => "2011" "volumen" => "39" "paginaInicial" => "257" "paginaFinal" => "265" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22783113" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0050" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Regulation of a phenylalanine ammonia lyase (BbPAL) by calmodulin in response to environmental changes in the entomopathogenic fungus <span class="elsevierStyleItalic">Beauveria bassiana</span>" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Kim" 1 => "H. Park" 2 => "J.G. Han" 3 => "J. Oh" 4 => "H.K. Choi" 5 => "S.H. Kim" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/1462-2920.12898" "Revista" => array:6 [ "tituloSerie" => "Environ Microbiol" "fecha" => "2015" "volumen" => "17" "paginaInicial" => "4484" "paginaFinal" => "4494" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25970691" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0055" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Calmodulin-mediated suppression of 2-ketoisovalerate reductase in <span class="elsevierStyleItalic">Beauveria bassiana</span> beauvericin biosynthetic pathway" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. Kim" 1 => "D.H. Yoon" 2 => "J. Oh" 3 => "M.W. Hyun" 4 => "J.G. Han" 5 => "G.H. Sung" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/1462-2920.13461" "Revista" => array:6 [ "tituloSerie" => "Environ Microbiol" "fecha" => "2016" "volumen" => "18" "paginaInicial" => "4136" "paginaFinal" => "4143" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27449895" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0060" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biological activities of beauvericin, a mini review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K. Kuca" 1 => "J. Patocka" 2 => "Q. Wu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2174/1389557518666180928161808" "Revista" => array:2 [ "tituloSerie" => "Mini Rev Med Chem" "fecha" => "2018" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0065" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CaMBOT: profiling and characterizing calmodulin binding proteins" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.H. O’Day" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0898-6568(02)00116-x" "Revista" => array:6 [ "tituloSerie" => "Cell Signal" "fecha" => "2003" "volumen" => "15" "paginaInicial" => "347" "paginaFinal" => "354" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12618209" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0070" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Coping with stresses: roles of calcium- and calcium/calmodulin-regulated gene expression" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.S. Reddy" 1 => "G.S. Ali" 2 => "H. Celesnik" 3 => "I.S. Day" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1105/tpc.111.084988" "Revista" => array:6 [ "tituloSerie" => "Plant Cell" "fecha" => "2011" "volumen" => "23" "paginaInicial" => "2010" "paginaFinal" => "2032" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21642548" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack434617" "titulo" => "Acknowledgements" "texto" => "<p id="par0030" class="elsevierStylePara elsevierViewall">This study was partially supported by the Individual Basic Research Support Project, the <span class="elsevierStyleGrantSponsor" id="gs1">National Research Foundation of Korea</span> (<span class="elsevierStyleGrantNumber" refid="gs1">NRF-2018R1D1A1B07051052</span>).</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/11301406/0000003600000003/v1_201911190704/S1130140619300403/v1_201911190704/en/main.assets" "Apartado" => array:4 [ "identificador" => "8081" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Carta a los Directores" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/11301406/0000003600000003/v1_201911190704/S1130140619300403/v1_201911190704/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1130140619300403?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 0 | 7 |
| 2024 October | 23 | 7 | 30 |
| 2024 September | 38 | 2 | 40 |
| 2024 August | 29 | 3 | 32 |
| 2024 July | 20 | 8 | 28 |
| 2024 June | 20 | 7 | 27 |
| 2024 May | 19 | 4 | 23 |
| 2024 April | 16 | 11 | 27 |
| 2024 March | 24 | 3 | 27 |
| 2024 February | 17 | 3 | 20 |
| 2024 January | 15 | 8 | 23 |
| 2023 December | 34 | 5 | 39 |
| 2023 November | 43 | 9 | 52 |
| 2023 October | 52 | 5 | 57 |
| 2023 September | 39 | 4 | 43 |
| 2023 August | 12 | 5 | 17 |
| 2023 July | 15 | 2 | 17 |
| 2023 June | 32 | 4 | 36 |
| 2023 May | 80 | 0 | 80 |
| 2023 April | 38 | 3 | 41 |
| 2023 March | 18 | 4 | 22 |
| 2023 February | 15 | 3 | 18 |
| 2023 January | 16 | 8 | 24 |
| 2022 December | 32 | 7 | 39 |
| 2022 November | 42 | 16 | 58 |
| 2022 October | 25 | 10 | 35 |
| 2022 September | 24 | 11 | 35 |
| 2022 August | 26 | 9 | 35 |
| 2022 July | 26 | 7 | 33 |
| 2022 June | 23 | 5 | 28 |
| 2022 May | 29 | 12 | 41 |
| 2022 April | 42 | 11 | 53 |
| 2022 March | 58 | 14 | 72 |
| 2022 February | 58 | 7 | 65 |
| 2022 January | 52 | 9 | 61 |
| 2021 December | 33 | 8 | 41 |
| 2021 November | 30 | 18 | 48 |
| 2021 October | 56 | 28 | 84 |
| 2021 September | 22 | 11 | 33 |
| 2021 August | 21 | 9 | 30 |
| 2021 July | 19 | 15 | 34 |
| 2021 June | 13 | 5 | 18 |
| 2021 May | 29 | 21 | 50 |
| 2021 April | 67 | 30 | 97 |
| 2021 March | 41 | 23 | 64 |
| 2021 February | 25 | 18 | 43 |
| 2021 January | 32 | 20 | 52 |
| 2020 December | 34 | 19 | 53 |
| 2020 November | 27 | 13 | 40 |
| 2020 October | 18 | 10 | 28 |
| 2020 September | 25 | 18 | 43 |
| 2020 August | 25 | 16 | 41 |
| 2020 July | 24 | 15 | 39 |
| 2020 May | 2 | 3 | 5 |
| 2020 April | 0 | 1 | 1 |
| 2020 March | 13 | 23 | 36 |
| 2020 February | 13 | 16 | 29 |
| 2020 January | 15 | 2 | 17 |
| 2019 December | 32 | 20 | 52 |
| 2019 November | 54 | 20 | 74 |
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