A human-specific modifier of cortical connectivity and circuit function.

The cognitive abilities that characterize humans are thought to emerge from unique features of the cortical circuit architecture of the human brain, which include increased cortico-cortical connectivity. However, the evolutionary origin of these changes in connectivity and how they affected cortical circuit function and behaviour are currently unknown. The human-specific gene duplication SRGAP2C emerged in the ancestral genome of the Homo lineage before the major phase of increase in brain size1,2. SRGAP2C expression in mice increases the density of excitatory and inhibitory synapses received by layer 2/3 pyramidal neurons (PNs)3-5. Here we show that the increased number of excitatory synapses received by layer 2/3 PNs induced by SRGAP2C expression originates from a specific increase in local and long-range cortico-cortical connections. Mice humanized for SRGAP2C expression in all cortical PNs displayed a shift in the fraction of layer 2/3 PNs activated by sensory stimulation and an enhanced ability to learn a cortex-dependent sensory-discrimination task. Computational modelling revealed that the increased layer 4 to layer 2/3 connectivity induced by SRGAP2C expression explains some of the key changes in sensory coding properties. These results suggest that the emergence of SRGAP2C at the birth of the Homo lineage contributed to the evolution of specific structural and functional features of cortical circuits in the human cortex.

Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity.

During 25 surveys of global Phytophthora diversity, conducted between 1998 and 2020, 43 new species were detected in natural ecosystems and, occasionally, in nurseries and outplantings in Europe, Southeast and East Asia and the Americas. Based on a multigene phylogeny of nine nuclear and four mitochondrial gene regions they were assigned to five of the six known subclades, 2a-c, e and f, of Phytophthora major Clade 2 and the new subclade 2g. The evolutionary history of the Clade appears to have involved the pre-Gondwanan divergence of three extant subclades, 2c, 2e and 2f, all having disjunct natural distributions on separate continents and comprising species with a soilborne and aquatic lifestyle and, in addition, a few partially aerial species in Clade 2c; and the post-Gondwanan evolution of subclades 2a and 2g in Southeast/East Asia and 2b in South America, respectively, from their common ancestor. Species in Clade 2g are soilborne whereas Clade 2b comprises both soil-inhabiting and aerial species. Clade 2a has evolved further towards an aerial lifestyle comprising only species which are predominantly or partially airborne. Based on high nuclear heterozygosity levels ca. 38 % of the taxa in Clades 2a and 2b could be some form of hybrid, and the hybridity may be favoured by an A1/A2 breeding system and an aerial life style. Circumstantial evidence suggests the now 93 described species and informally designated taxa in Clade 2 result from both allopatric non-adaptive and sympatric adaptive radiations. They represent most morphological and physiological characters, breeding systems, lifestyles and forms of host specialism found across the Phytophthora clades as a whole, demonstrating the strong biological cohesiveness of the genus. The finding of 43 previously unknown species from a single Phytophthora clade highlight a critical lack of information on the scale of the unknown pathogen threats to forests and natural ecosystems, underlining the risk of basing plant biosecurity protocols mainly on lists of named organisms. More surveys in natural ecosystems of yet unsurveyed regions in Africa, Asia, Central and South America are needed to unveil the full diversity of the clade and the factors driving diversity, speciation and adaptation in Phytophthora. Taxonomic novelties: New species: Phytophthora amamensis T. Jung, K. Kageyama, H. Masuya & S. Uematsu, Phytophthora angustata T. Jung, L. Garcia, B. Mendieta-Araica, & Y. Balci, Phytophthora balkanensis I. Milenkovic, Z. Tomic, T. Jung & M. Horta Jung, Phytophthora borneensis T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora calidophila T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora catenulata T. Jung, T.-T. Chang, N.M. Chi & M. Horta Jung, Phytophthora celeris T. Jung, L. Oliveira, M. Tarigan & I. Milenkovic, Phytophthora curvata T. Jung, A. Hieno, H. Masuya & M. Horta Jung, Phytophthora distorta T. Jung, A. Durán, E. Sanfuentes von Stowasser & M. Horta Jung, Phytophthora excentrica T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora falcata T. Jung, K. Kageyama, S. Uematsu & M. Horta Jung, Phytophthora fansipanensis T. Jung, N.M. Chi, T. Corcobado & C.M. Brasier, Phytophthora frigidophila T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora furcata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora inclinata N.M. Chi, T. Jung, M. Horta Jung & I. Milenkovic, Phytophthora indonesiensis T. Jung, M. Tarigan, L. Oliveira & I. Milenkovic, Phytophthora japonensis T. Jung, A. Hieno, H. Masuya & J.F. Webber, Phytophthora limosa T. Corcobado, T. Majek, M. Ferreira & T. Jung, Phytophthora macroglobulosa H.-C. Zeng, H.-H. Ho, F.-C. Zheng & T. Jung, Phytophthora montana T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora multipapillata T. Jung, M. Tarigan, I. Milenkovic & M. Horta Jung, Phytophthora multiplex T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora nimia T. Jung, H. Masuya, A. Hieno & C.M. Brasier, Phytophthora oblonga T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora obovoidea T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora obturata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora penetrans T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora platani T. Jung, A. Pérez-Sierra, S.O. Cacciola & M. Horta Jung, Phytophthora proliferata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora pseudocapensis T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pseudocitrophthora T. Jung, S.O. Cacciola, J. Bakonyi & M. Horta Jung, Phytophthora pseudofrigida T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora pseudoccultans T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pyriformis T. Jung, Y. Balci, K.D. Boders & M. Horta Jung, Phytophthora sumatera T. Jung, M. Tarigan, M. Junaid & A. Durán, Phytophthora transposita T. Jung, K. Kageyama, C.M. Brasier & H. Masuya, Phytophthora vacuola T. Jung, H. Masuya, K. Kageyama & J.F. Webber, Phytophthora valdiviana T. Jung, E. Sanfuentes von Stowasser, A. Durán & M. Horta Jung, Phytophthora variepedicellata T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora vietnamensis T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora ×australasiatica T. Jung, N.M. Chi, M. Tarigan & M. Horta Jung, Phytophthora ×lusitanica T. Jung, M. Horta Jung, C. Maia & I. Milenkovic, Phytophthora ×taiwanensis T. Jung, T.-T. Chang, H.-S. Fu & M. Horta Jung. Citation: Jung T, Milenkovic I, Balci Y, Janousek J, Kudlácek T, Nagy ZÁ, Baharuddin B, Bakonyi J, Broders KD, Cacciola SO, Chang T-T, Chi NM, Corcobado T, Cravador A, Dordevic B, Durán A, Ferreira M, Fu C-H, Garcia L, Hieno A, Ho H-H, Hong C, Junaid M, Kageyama K, Kuswinanti T, Maia C, Májek T, Masuya H, Magnano di San Lio G, Mendieta-Araica B, Nasri N, Oliveira LSS, Pane A, Pérez-Sierra A, Rosmana A, Sanfuentes von Stowasser E, Scanu B, Singh R, Stanivukovic Z, Tarigan M, Thu PQ, Tomic Z, Tomsovský M, Uematsu S, Webber JF, Zeng H-C, Zheng F-C, Brasier CM, Horta Jung M (2024). Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity. Studies in Mycology 107: 251-388. doi: 10.3114/sim.2024.107.04.

Assessment of the stallion sperm acrosome in two different extenders: Spermac stain in comparison with PNA/PSA/PI triple-staining.

Since the stallion acrosome is very small compared to other species and cannot be properly assessed without additional staining, several labelling techniques were developed to facilitate its assessment. The aim of this study was to compare the Spermac stain (Minitüb GmbH) and a PNA/PSA/PI triple-staining detected by flow cytometry with regard to method agreement for detecting non-intact acrosomes within two different extenders. For this purpose, eighteen stallion ejaculates were split in half and diluted with the semen extenders EquiPlus or Gent (Minitüb GmbH) to a final concentration of 50 × 106 sperm/mL, respectively. Subsequently, 126 semen samples were stained with both methods between 4 and 240 h (mean: 63.8 ± 48.9 h) after semen collection. Calculated Intraclass correlation coefficients revealed excellent correlations between both methods for EquiPlus (r = .77, p < .001) and fair correlations for Gent (r = .49, p < .001). Interestingly, flow cytometry detected more non-intact acrosomes in EquiPlus than in Gent (p < .001), whereas the Spermac stain showed no differences (p = .902) between extenders. The poorer method agreement in Gent could be caused by egg yolk artefacts, which made interpretation difficult, so flow cytometry might be preferred. The differences in detected non-intact acrosomes between extenders highlighted the importance of establishing adapted laboratory protocols for different extender types in order to generate comparable results.

Rotation of liquid-preserved artificial insemination doses on roller benches affects sperm quality during storage in stallions.

Appropriate stallion semen handling is of great importance in equine artificial insemination (AI) industry. Optimal treatment of AI doses is aiming for best sperm preservation by excluding strong environmental influences and adding media that favour sperm survival. One method widely used in stallion sperm handling is the rotation of liquid-preserved semen samples on roller benches during storage. As previous studies in boars give rise to the fact that rotation should not be considered beneficial for spermatozoa anymore, the present study investigated the influence of continuous rotation of diluted stallion AI portions on sperm quality. Ejaculates (n = 15) were collected at a German AI centre and diluted with the two extenders EquiPlus and Gent (Minitüb GmbH) to a final concentration of 50 × 106 sperm/mL. Afterwards, samples were placed separately on roller benches at 5°C in the dark, obtaining a rotation frequency of 5 revolutions per minute (rpm) and 36 rpm for four consecutive days following a split-sample design. Both groups were analysed daily in comparison to a control group (0 rpm) with an extended spectrum of spermatological methods including computer-assisted sperm analysis and flow cytometry. Statistical analyses were based on the calculation of generalized linear mixed models for each sperm parameter. The research revealed a decrease in sperm quality parameters of rotated samples compared to non-rotated control groups, visible in total sperm motility (p < .001), decreased thermo-resistance (p < .01) and a drop in pH (p < .001). Interestingly, no differences (p > .05) were detected between rotation frequencies of 5 and 36 rpm. We conclude that the fertilizing capacity of stallion semen was negatively affected by rotation during storage in vitro, irrespective of the rotation frequency. Further studies need to investigate whether field fertility in horses is similarly affected by semen rotation on roller benches in vivo.

Suggested use of empirical antibiotics in acute cholecystitis based on bile microbiology and antibiotic susceptibility.

BACKGROUND: Bacterial infection is common in acute cholecystitis (AC). To identify appropriate empirical antibiotics, we investigated AC-associated microorganisms and their susceptibilities to antibiotics. We also compared preoperative clinical findings of patients grouped according to specific microorganisms. METHODS: Patients who underwent laparoscopic cholecystectomy for AC between 2018 and 2019 were enrolled. Bile cultures and antibiotic susceptibility tests were performed, and clinical findings of patients were noted. RESULTS: A total of 282 patients were enrolled (147 culture-positive and 135 culture-negative). The most frequent microorganisms were Escherichia (n = 53, 32.7%), Enterococcus (n = 37, 22.8%), Klebsiella (n = 28, 17.3%), and Enterobacter (n = 18, 11.1%). For Gram-negative microorganisms, second-generation cephalosporin (cefotetan: 96.2%) was more effective than third-generation cephalosporin (cefotaxime: 69.8%). Vancomycin and teicoplanin (83.8%) were the most effective antibiotics for Enterococcus. Patients with Enterococcus had higher rates of CBD stones (51.4%, p = 0.001) and biliary drainage (81.1%, p = 0.002), as well as higher levels of liver enzymes, than patients with other microorganisms. Patients with ESBL-producing bacteria had higher rates of CBD stones (36.0% vs. 6.8%, p = 0.001) and biliary drainage (64.0% vs. 32.4%, p = 0.005) than those without. DISCUSSION: Preoperative clinical findings of AC are related to microorganisms in bile samples. Periodic antibiotic susceptibility tests should be conducted to select appropriate empirical antibiotics.

Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model.

Resident cardiac macrophages (rcMACs) are among the most abundant immune cells in the heart. Plasticity and activation are hallmarks of rcMACs in response to changes in the microenvironment, which is essential for in vitro experimentation. The in vivo investigation is confounded by the infiltration of other cells hindering direct studies of rcMACs. As a tool to investigate rcMACs, we applied the ex vivo model of living myocardial slices (LMS). LMS are ultrathin ex vivo multicellular cardiac preparations in which the circulatory network is interrupted. The absence of infiltration in this model enables the investigation of the rcMACs response to immunomodulatory and mechanical stimulations. Such conditions were generated by applying interferon-gamma (IFN-γ) or interleukine-4 (IL-4) and altering the preload of cultured LMS, respectively. The immunomodulatory stimulation of the LMS induced alterations of the gene expression pattern without affecting tissue contractility. Following 24 h culture, low input RNA sequencing of rcMACs isolated from LMS was used for gene ontology analysis. Reducing the tissue stretch (unloading) of LMS altered the gene ontology clusters of isolated rcMACs with intermediate semantic similarity to IFN-γ triggered reaction. Through the overlap of genes affected by IFN-γ and unloading, we identified Allograft inflammatory factor 1 (AIF-1) as a potential marker gene for inflammation of rcMACs as significantly altered in whole immunomodulated LMS. MicroRNAs associated with the transcriptomic changes of rcMACs in unloaded LMS were identified in silico. Here, we demonstrate the approach of LMS to understand load-triggered cardiac inflammation and, thus, identify potential translationally important therapeutic targets.

Genera of phytopathogenic fungi: GOPHY 4.

This paper is the fourth contribution in the Genera of Phytopathogenic Fungi (GOPHY) series. The series provides morphological descriptions and information about the pathology, distribution, hosts and disease symptoms, as well as DNA barcodes for the taxa covered. Moreover, 12 whole-genome sequences for the type or new species in the treated genera are provided. The fourth paper in the GOPHY series covers 19 genera of phytopathogenic fungi and their relatives, including Ascochyta, Cadophora, Celoporthe, Cercospora, Coleophoma, Cytospora, Dendrostoma, Didymella, Endothia, Heterophaeomoniella, Leptosphaerulina, Melampsora, Nigrospora, Pezicula, Phaeomoniella, Pseudocercospora, Pteridopassalora, Zymoseptoria, and one genus of oomycetes, Phytophthora. This study includes two new genera, 30 new species, five new combinations, and 43 typifications of older names. Taxonomic novelties: New genera: Heterophaeomoniella L. Mostert, C.F.J. Spies, Halleen & Gramaje, Pteridopassalora C. Nakash. & Crous; New species: Ascochyta flava Qian Chen & L. Cai, Cadophora domestica L. Mostert, R. van der Merwe, Halleen & Gramaje, Cadophora rotunda L. Mostert, R. van der Merwe, Halleen & Gramaje, Cadophora vinacea J.R. Úrbez-Torres, D.T. O'Gorman & Gramaje, Cadophora vivarii L. Mostert, Havenga, Halleen & Gramaje, Celoporthe foliorum H. Suzuki, Marinc. & M.J. Wingf., Cercospora alyssopsidis M. Bakhshi, Zare & Crous, Dendrostoma elaeocarpi C.M. Tian & Q. Yang, Didymella chlamydospora Qian Chen & L. Cai, Didymella gei Qian Chen & L. Cai, Didymella ligulariae Qian Chen & L. Cai, Didymella qilianensis Qian Chen & L. Cai, Didymella uniseptata Qian Chen & L. Cai, Endothia cerciana W. Wang. & S.F. Chen, Leptosphaerulina miscanthi Qian Chen & L. Cai, Nigrospora covidalis M. Raza, Qian Chen & L. Cai, Nigrospora globospora M. Raza, Qian Chen & L. Cai, Nigrospora philosophiae-doctoris M. Raza, Qian Chen & L. Cai, Phytophthora transitoria I. Milenkovic, T. Májek & T. Jung, Phytophthora panamensis T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora variabilis T. Jung, M. Horta Jung & I. Milenkovic, Pseudocercospora delonicicola C. Nakash., L. Suhaizan & I. Nurul Faziha, Pseudocercospora farfugii C. Nakash., I. Araki, & Ai Ito, Pseudocercospora hardenbergiae Crous & C. Nakash., Pseudocercospora kenyirana C. Nakash., L. Suhaizan & I. Nurul Faziha, Pseudocercospora perrottetiae Crous, C. Nakash. & C.Y. Chen, Pseudocercospora platyceriicola C. Nakash., Y. Hatt, L. Suhaizan & I. Nurul Faziha, Pseudocercospora stemonicola C. Nakash., Y. Hatt., L. Suhaizan & I. Nurul Faziha, Pseudocercospora terengganuensis C. Nakash., Y. Hatt., L. Suhaizan & I. Nurul Faziha, Pseudocercospora xenopunicae Crous & C. Nakash.; New combinations: Heterophaeomoniella pinifoliorum (Hyang B. Lee et al.) L. Mostert, C.F.J. Spies, Halleen & Gramaje, Pseudocercospora pruni-grayanae (Sawada) C. Nakash. & Motohashi., Pseudocercospora togashiana (K. Ito & Tak. Kobay.) C. Nakash. & Tak. Kobay., Pteridopassalora nephrolepidicola (Crous & R.G. Shivas) C. Nakash. & Crous, Pteridopassalora lygodii (Goh & W.H. Hsieh) C. Nakash. & Crous; Typification: Epitypification: Botrytis infestans Mont., Cercospora abeliae Katsuki, Cercospora ceratoniae Pat. & Trab., Cercospora cladrastidis Jacz., Cercospora cryptomeriicola Sawada, Cercospora dalbergiae S.H. Sun, Cercospora ebulicola W. Yamam., Cercospora formosana W. Yamam., Cercospora fukuii W. Yamam., Cercospora glochidionis Sawada, Cercospora ixorana J.M. Yen & Lim, Cercospora liquidambaricola J.M. Yen, Cercospora pancratii Ellis & Everh., Cercospora pini-densiflorae Hori & Nambu, Cercospora profusa Syd. & P. Syd., Cercospora pyracanthae Katsuki, Cercospora horiana Togashi & Katsuki, Cercospora tabernaemontanae Syd. & P. Syd., Cercospora trinidadensis F. Stevens & Solheim, Melampsora laricis-urbanianae Tak. Matsumoto, Melampsora salicis-cupularis Wang, Phaeoisariopsis pruni-grayanae Sawada, Pseudocercospora angiopteridis Goh & W.H. Hsieh, Pseudocercospora basitruncata Crous, Pseudocercospora boehmeriigena U. Braun, Pseudocercospora coprosmae U. Braun & C.F. Hill, Pseudocercospora cratevicola C. Nakash. & U. Braun, Pseudocercospora cymbidiicola U. Braun & C.F. Hill, Pseudocercospora dodonaeae Boesew., Pseudocercospora euphorbiacearum U. Braun, Pseudocercospora lygodii Goh & W.H. Hsieh, Pseudocercospora metrosideri U. Braun, Pseudocercospora paraexosporioides C. Nakash. & U. Braun, Pseudocercospora symploci Katsuki & Tak. Kobay. ex U. Braun & Crous, Septogloeum punctatum Wakef.; Neotypification: Cercospora aleuritis I. Miyake; Lectotypification: Cercospora dalbergiae S.H. Sun, Cercospora formosana W. Yamam., Cercospora fukuii W. Yamam., Cercospora glochidionis Sawada, Cercospora profusa Syd. & P. Syd., Melampsora laricis-urbanianae Tak. Matsumoto, Phaeoisariopsis pruni-grayanae Sawada, Pseudocercospora symploci Katsuki & Tak. Kobay. ex U. Braun & Crous. Citation: Chen Q, Bakhshi M, Balci Y, Broders KD, Cheewangkoon R, Chen SF, Fan XL, Gramaje D, Halleen F, Horta Jung M, Jiang N, Jung T, Májek T, Marincowitz S, Milenkovic T, Mostert L, Nakashima C, Nurul Faziha I, Pan M, Raza M, Scanu B, Spies CFJ, Suhaizan L, Suzuki H, Tian CM, Tomsovský M, Úrbez-Torres JR, Wang W, Wingfield BD, Wingfield MJ, Yang Q, Yang X, Zare R, Zhao P, Groenewald JZ, Cai L, Crous PW (2022). Genera of phytopathogenic fungi: GOPHY 4. Studies in Mycology 101: 417-564. doi: 10.3114/sim.2022.101.06.

Targeted PMP22 TATA-box editing by CRISPR/Cas9 reduces demyelinating neuropathy of Charcot-Marie-Tooth disease type 1A in mice.

Charcot-Marie-Tooth 1A (CMT1A) is the most common inherited neuropathy without a known therapy, which is caused by a 1.4 Mb duplication on human chromosome 17, which includes the gene encoding the peripheral myelin protein of 22 kDa (PMP22). Overexpressed PMP22 protein from its gene duplication is thought to cause demyelination and subsequently axonal degeneration in the peripheral nervous system (PNS). Here, we targeted TATA-box of human PMP22 promoter to normalize overexpressed PMP22 level in C22 mice, a mouse model of CMT1A harboring multiple copies of human PMP22. Direct local intraneural delivery of CRISPR/Cas9 designed to target TATA-box of PMP22 before the onset of disease, downregulates gene expression of PMP22 and preserves both myelin and axons. Notably, the same approach was effective in partial rescue of demyelination even after the onset of disease. Collectively, our data present a proof-of-concept that CRISPR/Cas9-mediated targeting of TATA-box can be utilized to treat CMT1A.

Eight new Halophytophthora species from marine and brackish-water ecosystems in Portugal and an updated phylogeny for the genus.

During an oomycete survey in December 2015, 10 previously unknown Halophytophthora taxa were isolated from marine and brackish water of tidal ponds and channels in saltmarshes, lagoon ecosystems and river estuaries at seven sites along the Algarve coast in the South of Portugal. Phylogenetic analyses of LSU and ITS datasets, comprising all described Halophytophthora species, the 10 new Halophytophthora taxa and all relevant and distinctive sequences available from GenBank, provided an updated phylogeny of the genus Halophytophthora s.str. showing for the first time a structure of 10 clades designated as Clades 1-10. Nine of the 10 new Halophytophthora taxa resided in Clade 6 together with H. polymorphica and H. vesicula. Based on differences in morphology and temperature-growth relations and a multigene (LSU, ITS, Btub, hsp90, rpl10, tigA, cox1, nadh1, rps10) phylo-geny, eight new Halophytophthora taxa from Portugal are described here as H. brevisporangia, H. cele-ris, H. frigida, H. lateralis, H. lusitanica, H. macrosporangia, H. sinuata and H. thermoambigua. Three species, H. frigida, H. macrosporangia and H. sinuata, have a homothallic breeding system while the remaining five species are sterile. Pathogenicity and litter decomposition tests are underway to clarify their pathological and ecological role in the marine and brackish-water ecosystems. More oomycete surveys in yet undersurveyed regions of the world and population genetic or phylogenomic analyses of global populations are needed to clarify the origin of the new Halophytophthora species. Citation: Maia C, Horta Jung M, Carella G, et al. 2022. Eight new Halophytophthora species from marine and brackish-water ecosystems in Portugal and an updated phylogeny for the genus. Persoonia 48: 54 - 90. https://doi.org/10.3767/persoonia.2022.48.02..

Extensive morphological and behavioural diversity among fourteen new and seven described species in Phytophthora Clade 10 and its evolutionary implications.

During extensive surveys of global Phytophthora diversity 14 new species detected in natural ecosystems in Chile, Indonesia, USA (Louisiana), Sweden, Ukraine and Vietnam were assigned to Phytophthora major Clade 10 based on a multigene phylogeny of nine nuclear and three mitochondrial gene regions. Clade 10 now comprises three subclades. Subclades 10a and 10b contain species with nonpapillate sporangia, a range of breeding systems and a mainly soil- and waterborne lifestyle. These include the previously described P. afrocarpa, P. gallica and P. intercalaris and eight of the new species: P. ludoviciana, P. procera, P. pseudogallica, P. scandinavica, P. subarctica, P. tenuimura, P. tonkinensis and P. ukrainensis. In contrast, all species in Subclade 10c have papillate sporangia and are self-fertile (or homothallic) with an aerial lifestyle including the known P. boehmeriae, P. gondwanensis, P. kernoviae and P. morindae and the new species P. celebensis, P. chilensis, P. javanensis, P. multiglobulosa, P. pseudochilensis and P. pseudokernoviae. All new Phytophthora species differed from each other and from related species by their unique combinations of morphological characters, breeding systems, cardinal temperatures and growth rates. The biogeography and evolutionary history of Clade 10 are discussed. We propose that the three subclades originated via the early divergence of pre-Gondwanan ancestors > 175 Mya into water- and soilborne and aerially dispersed lineages and subsequently underwent multiple allopatric and sympatric radiations during their global spread. Citation: Jung T, Milenkovic I, Corcobado T, et al. 2022. Extensive morphological and behavioural diversity among fourteen new and seven described species in Phytophthora Clade 10 and its evolutionary implications. Persoonia 49: 1-57. https://doi.org/10.3767/persoonia.2022.49.01.

Resident cardiac macrophages: crucial modulators of cardiac (patho)physiology.

Resident cardiac macrophages (rcMacs) are integral components of the myocardium where they have key roles for tissue homeostasis and in response to inflammation, tissue injury and remodelling. In this review, we summarize the current knowledge and limitations associated with the rcMacs studies. We describe their specific role and contribution in various processes such as electrical conduction, efferocytosis, inflammation, tissue development, remodelling and regeneration in both the healthy and the disease state. We also outline research challenges and technical complications associated with rcMac research. Recent technological developments and contemporary immunological techniques are now offering new opportunities to investigate the separate contribution of rcMac in respect to recruited monocytes and other cardiac cells. Finally, we discuss new therapeutic strategies, such as drugs or non-coding RNAs, which can influence rcMac phenotype and their response to inflammation. These novel approaches will allow for a deeper understanding of this cardiac endogenous cell type and might lead to the development of more specific and effective therapeutic strategies to boost the heart's intrinsic reparative capacity.

Laparoscopic sentinel node navigation surgery versus laparoscopic gastrectomy with lymph node dissection for early gastric cancer: short-term outcomes of a multicentre randomized controlled trial (SENORITA).

BACKGROUND: Sentinel node navigation surgery reduces the extent of gastric and lymph node dissection, and may improve quality of life. The benefit and harm of laparoscopic sentinel node navigation surgery (LSNNS) for early gastric cancer is unknown. The SENORITA (SEntinel Node ORIented Tailored Approach) trial investigated the pathological and surgical outcomes of LSNNS compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection. METHODS: The SENORITA trial was an investigator-initiated, open-label, parallel-assigned, non-inferiority, multicentre RCT conducted in Korea. The primary endpoint was 3-year disease-free survival. The secondary endpoints, morbidity and mortality within 30 days of surgery, are reported in the present study. RESULTS: A total of 580 patients were randomized to LSG (292) or LSNNS (288). Surgery was undertaken in 527 patients (LSG 269, LSNNS 258). LSNNS could be performed according to the protocol in 245 of 258 patients, and a sentinel node basin was detected in 237 (96·7 per cent) Stomach-preserving surgery was carried out in 210 of 258 patients (81·4 per cent). Postoperative complications occurred in 51 patients in the LSG group (19·0 per cent) and 40 (15·5 per cent) in the LSNNS group (P = 0·294). Complications with a Clavien-Dindo grade of III or higher occurred in 16 (5·9 per cent) and 13 (5·0 per cent) patients in the LSG and LSNNS groups respectively (P = 0·647). CONCLUSION: The rate and severity of complications following LSNNS for early gastric cancer are comparable to those after LSG with lymph node dissection. Registration number: NCT01804998 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La cirugía de navegación del ganglio centinela (sentinel node navigation surgery, SNNS) reduce la extensión de la resección gástrica y ganglionar, y puede mejorar la calidad de vida. Se desconoce el beneficio y el daño de la cirugía de navegación del ganglio centinela por vía laparoscópica (laparoscopic sentinel node navigation surgery, LSNNS) para el cáncer gástrico precoz. El ensayo clínico SENORITA investigó los resultados patológicos y quirúrgicos de LSNNS en comparación con la gastrectomía laparoscópica estándar (laparoscopic gastrectomy, LSG) con disección ganglionar (lymph node dissection, LND). MÉTODOS: El ensayo SENORITA fue un ensayo multicéntrico aleatorizado y controlado, iniciado por investigadores, abierto, con asignación a grupos paralelos y de no inferioridad llevado a cabo en Corea. El resultado primario fue la supervivencia libre de enfermedad a los 3 años. En el presente estudio, se describen los resultados secundarios correspondientes a morbilidad y mortalidad a los 30 días del postoperatorio. RESULTADOS: Un total de 580 pacientes fueron aleatorizados a LG (n = 292) o LSNNS (n = 288). La cirugía se realizó en 527 pacientes (LG 269, LSNNS 258). LSNNS pudo ser realizada de acuerdo con el protocolo en 245 de 258 pacientes y en 237 de 245 pacientes (96,7%) se detectó un ganglio centinela. La cirugía con preservación del estómago se realizó en 210 de 258 pacientes (81,4%). Las complicaciones postoperatorias se presentaron en 51 pacientes del grupo LSG (19,0%) y en 40 pacientes (15,5%) del grupo LSNNS (P = 0,294). Las complicaciones grado III o mayor de Clavien-Dindo se detectaron en 16 (5,9%) y 13 pacientes (5,0%) de los grupos LSG y LSNNS, respectivamente (P = 0,647). CONCLUSIÓN: El porcentaje y la gravedad de las complicaciones tras LSNNS para cancer gástrico precoz son comparables a la LSG con LND.

Cardiorespiratory fitness and accelerometer-determined physical activity following one year of free-living high-intensity interval training and moderate-intensity continuous training: a randomized trial.

BACKGROUND: Free-living adherence to high-intensity interval training (HIIT) has not been adequately tested. This randomized trial examined changes in cardiorespiratory fitness (CRF) and accelerometer-measured purposeful physical activity over 12 months of free-living HIIT versus moderate-intensity continuous training (MICT). METHODS: Ninety-nine previously low-active participants with overweight/obesity were randomly assigned to HIIT (n = 47) or MICT (n = 52). Both interventions were combined with evidence-based behaviour change counselling consisting of 7 sessions over 2 weeks. Individuals in HIIT were prescribed 10 X 1-min interval-based exercise 3 times per week (totalling 75 min) whereas individuals in MICT were prescribed 150 min of steady-state exercise per week (50 mins 3 times per week). Using a maximal cycling test to exhaustion with expired gas analyses, CRF was assessed at baseline and after 6 and 12 months of free-living exercise. Moderate-to-vigorous physical activity of 10+ minutes (MVPA10+) was assessed by 7-day accelerometry at baseline, 3, 6, 9, and 12 months. Intention to treat analyses were conducted using linear mixed models. RESULTS: CRF was improved over the 12 months relative to baseline in both HIIT (+ 0.15 l/min, 95% CI 0.08 to 0.23) and MICT (+ 0.11 l/min, 95% CI 0.05 to 0.18). Both groups improved 12-month MVPA10+ above baseline (HIIT: + 36 min/week, 95% CI 17 to 54; MICT: + 69 min/week, 95% CI 49 to 89) with the increase being greater (by 33 min, 95% CI 6 to 60) in MICT (between group difference, P = 0.018). CONCLUSION: Despite being prescribed twice as many minutes of exercise and accumulating significantly more purposeful exercise, CRF improvements were similar across 12 months of free-living HIIT and MICT in previously low-active individuals with overweight/obesity.

A novel bungarotoxin binding site-tagged construct reveals MAPK-dependent Kv4.2 trafficking.

Kv4.2 voltage-gated K+ channel subunits, the primary source of the somatodendritic A-type K+ current in CA1 pyramidal neurons of the hippocampus, play important roles in regulating dendritic excitability and plasticity. To better study the trafficking and subcellular distribution of Kv4.2, we created and characterized a novel Kv4.2 construct encoding a bungarotoxin binding site in the extracellular S3-S4 linker region of the α-subunit. When expressed, this construct can be visualized in living cells after staining with rhodamine-conjugated bungarotoxin. We validated the utility of this construct by visualizing the spontaneous internalization and insertion of Kv4.2 in HEK 293T cells. We further report that Kv4.2 colocalized with several endosome markers in HEK 293T cells. In addition, Kv4.2 internalization is significantly impaired by mitogen-activated protein kinase (MAPK) inhibitors in transfected primary hippocampal neurons. Therefore, this newly developed BBS-Kv4.2 construct provides a novel and powerful tool for studying surface Kv4.2 channel localization and trafficking.

Development of ICNP-based inpatient falls prevention catalogue.

OBJECTIVES: The International Council of Nurses supports the development of International Classification for Nursing Practice® (ICNP®) catalogues to support the construction of electronic health records and evidence-based practice. Such a catalogue is needed for inpatient falls. METHODS: The ICNP®-Based Inpatient Fall-Prevention Catalogue ('The Catalogue') was developed following the six steps recommended by the International Council of Nurses: (1) identifying inpatient falls as a priority, (2) gathering relevant concepts from 10 international guidelines and comparing locally defined sets of fall-prevention terms, (3) mapping the concepts to the ICNP® terminology, (4) identifying new concepts, (5) conducting a clinical face validation with a 12-member panel and finalizing The Catalogue and (6) setting a strategy for dissemination. The high-level structure of the International Classification for Patient Safety was used as a theoretical framework. RESULTS: Eighteen nursing care elements and 141 terms were identified. A local vocabulary set had 89 terms (63.1%) that all corresponded to the identified terms. The exact and post-coordination mapping rates to the ICNP® were 75% and 40.6% for assessment/diagnosis/outcomes and interventions, respectively. The 54 new terms corresponded to 52 primitive concepts. An external review of The Catalogue showed that it had adequate understandability and validity. However, one-third of assessments/diagnoses/outcomes and one-fourth of interventions were not found in a tertiary hospital practice. CONCLUSION: A fall-prevention catalogue has been developed based on evidence and a theoretical framework and also clinically validated. IMPLICATION FOR NURSING AND HEALTH POLICY: The Catalogue is a standardized interface terminology and content subset in any electronic health records system that can directly deliver evidence on fall prevention. It can also be used as an informatics tool to aggregate, analyse, interpret and compare nursing data worldwide.

Novel and Private EDA Mutations and Clinical Phenotypes of Korean Patients with X-Linked Hypohidrotic Ectodermal Dysplasia.

X-linked hypohidrotic ectodermal dysplasia (XLHED; OMIM 305100) is the most common form of ectodermal dysplasia, presenting with the triad of hypotrichosis, hypodontia, and hypohidrosis. This disorder is caused by mutations in EDA, which encodes ectodysplasin A, a member of the tumor necrosis factor superfamily. In this study, we describe clinical and genetic characteristics of 10 Korean XLHED patients (9 males, 1 female) from 9 families. Nine out of the 10 patients manifested the cardinal triad of symptoms. Six patients had a positive family history, while 2 patients were brothers. The most common initial presentation was hypotrichosis or hypodontia, while 1 patient presented with recurrent high fever in early infancy. Sanger sequencing of the EDA gene was performed and revealed 9 different mutations. Three had been reported previously, and 6 were novel mutations. One female patient, carrying a previously reported missense mutation, might be affected by skewed X-inactivation. This is the first observational study investigating genetically confirmed XLHED patients in Korea. To provide appropriate supportive care and genetic counseling, clinicians should consider the possibility of XLHED in the differential diagnosis of recurrent fever in infants, as well as recognize the typical triad of symptoms.

Favorable outcomes of culture-based Helicobacter pylori eradication therapy in a region with high antimicrobial resistance.

BACKGROUND: The eradication rate of Helicobacter pylori has declined, mainly due to antimicrobial resistance. To overcome resistance-associated treatment failure, the efficacy of culture-based, susceptibility-guided therapy was demonstrated as the first-line eradication therapy for H pylori infection. AIMS: To evaluate the efficacy of culture-based therapy as the first-line eradication therapy in regions with high levels of antimicrobial resistance. METHODS: Helicobacter pylori-positive patients without previous eradication treatment history were recommended to undergo culture to determine the minimal inhibitory concentration (MIC). If they consented, 7-day clarithromycin-containing PPI triple; 7-day esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; or 7- or 14-day esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy were administered based on the agar dilution-determined MIC. Eradication, treatment compliance, and adverse events were examined. RESULTS: In total, 74 patients were enrolled, and 69 patients completed the protocols. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 6.7%, 31.0%, 41.8%, and 39.2%, respectively. The patients were allocated to the PPI triple (n = 50), MEA (n = 8) or quadruple (n = 16) therapy. The eradication rate in the intention-to-treat analysis was 93.1% (69 of 74 patients). The eradication rates in the per-protocol analysis were 100.0% (69 of 69 patients). Epigastric pain, nausea, and vomiting were less common than those of other empirical therapies. CONCLUSIONS: Culture-based, susceptibility-guided therapy is effective first-line eradication therapy, especially in regions with high levels of antimicrobial resistance.

[Arthroplasty of the TMT1 joint-a critical view]. / Daumensattelgelenkendoprothetik ­ eine kritische Beurteilung.

Resection suspension arthroplasty of the trapezium still represents the golden standard in treatment of CMC 1 arthritis. First reports about long-term results of a modern-design endoprosthesis of the CMC 1 joint promise a lower complication and revision rate. Thus, endoprosthesis of the CMC1 joint is becoming more attractive, especially because the rehabilitation and back-to-work times are much faster. While new anatomic prosthesis designs are coming onto the market, which theoretically are less susceptible to loosening and dislocation, they still have to prove their superiority in the clinical setting.

[Anatomy of the trapeziometacarpal joint in the context of arthroplasty]. / Anatomie des Daumensattelgelenks unter Berücksichtigung der Endoprothetik.

The thumb has a crucial role in the hand due to its position with regard to the fingers. The CMC-1 joint enables an extraordinary range of motion, since its geometry allows for opposition. The former joint may often succumb to osteoarthritis because a great range of motion in combination with large forces, small contact areas, and thorough usage are always present. Joint replacement is challenged by the great range of motion based on the necessary joint stability and the demand for sufficient pain reduction. This review highlights the anatomy of the CMC-1 joint with regard to joint preplacement solutions.