Cognitive control is proposed to rely on a rostral-to-caudal hierarchy of neural processing within the prefrontal cortex (PFC), with more rostral parts exerting control over more caudal parts. ...Anatomical and functional data suggest that this hierarchical organization of the PFC may be separated into a ventral and a dorsal component. Furthermore, recent studies indicate that the apex of the hierarchy resides within the mid-lateral rather the rostral PFC. However, investigating the hierarchical aspect of rostro-to-caudal processing requires quantification of the directed interactions between PFC regions.
Using functional near-infrared spectroscopy (fNIRS) in a sample of healthy young adults we analyzed directed interactions between rostral and caudal PFC during passive watching of nature documentaries. Directed coherence (DC) as a measure of directed interaction was computed pairwise between 38 channels evenly distributed over the lateral prefrontal convexity.
Results revealed an overall predominance of rostral-to-caudal directed interactions in the PFC that further dissociated along a ventro-dorsal axis: Dorsal regions exerted stronger rostro-caudally directed interactions on dorsal than on ventral regions and vice versa. Interactions between ventral and dorsal PFC were stronger from ventral to dorsal areas than vice versa. Results further support the notion that the mid-dorsolateral PFC constitutes the apex of the prefrontal hierarchy.
Taken together these data provide novel evidence for parallel dorsal and ventral streams within the rostro-caudal hierarchical organization of the PFC. FNIRS-based analyses of directed interactions put forward a new perspective on the functional architecture of the prefrontal hierarchy and complement previous insights from functional magnetic resonance imaging.
•Near-infrared spectroscopy (NIRS) allows inference of directed functional networks.•NIRS reveals rostro-caudally directed interactions in prefrontal cortex (PFC).•Rostro-caudally directed interactions are segregated in a dorsal and ventral stream.•Rostro-caudal directed interactions peak in mid-dorsolateral PFC as apex of control.•NIRS-based analyses complement evidence from functional magnetic resonance imaging.
Summary
Botrytis cinerea is the causal agent of gray mold disease in various plant species and produces grayish macroconidia and/or black sclerotia at the end of the infection cycle. It has been ...suggested that the pigmentation is due to the accumulation of 1,8‐dihydroxynaphthalene (DHN) melanin. To unravel its basis and regulation, the putative melanogenic and regulatory genes were identified and functionally characterized. Unlike other DHN melanin‐producing fungi, B. cinerea and other Leotiomycetes contain two key enzyme (PKS)‐encoding enzymes. Bcpks12 and bcpks13 are developmentally regulated and are required for melanogenesis in sclerotia and conidia respectively. BcYGH1 converts the BcPKS13 product and contributes thereby to conidial melanogenesis. In contrast, enzymes acting downstream in conversion of the PKS products (BcBRN2, BcSCD1 and BcBRN1) are required for both, sclerotial and conidial melanogenesis, suggesting that DHN melanogenesis in B. cinerea follows a non‐linear pathway that is rather unusual for secondary metabolic pathways. Regulation of the melanogenic genes involves three pathway‐specific transcription factors (TFs) that are clustered with bcpks12 or bcpks13 and other developmental regulators such as light‐responsive TFs. Melanogenic genes are dispensable in vegetative mycelia for proper growth and virulence. However, DHN melanin is considered to contribute to the longevity of the reproduction structures.
Many black fungi produce the dark pigment 1,8‐dihydroxynaphthalene (DHN) melanin, often in a spatially and/or temporarily regulated manner. In the gray mold fungus Botrytis cinerea, DHN melanin is produced by a non‐linear/ converging biosynthetic pathway. The fungus contains two versions of the key enzyme (PKS; polyketide synthase) that are differentially expressed in conidia and sclerotia providing there the precursor for the subsequent conversion to DHN by the same enzymes.
•Botrytis cinerea is an aggressive plant pathogen causing gray mold diseases.•Near-UV, blue, green, red and far-red light affect its growth characteristics.•Eleven (plus X?) potential photoreceptors ...cover the entire light spectrum.•A sophisticated signaling machinery allows for processing the light signals.•Light regulates morphogenesis, tropism, entrainment and stress responses.
Fungi, like other organisms, actively sense the environmental light conditions in order to drive adaptive responses, including protective mechanisms against the light-associated stresses, and to regulate development. Ecological niches are characterized by different light regimes, for instance light is absent underground, and light spectra from the sunlight are changed underwater or under the canopy of foliage due to the absorption of distinct wavelengths by bacterial, algal and plant pigments. Considering the fact that fungi have evolved to adapt to their habitats, the complexities of their ‘visual’ systems may vary significantly. Fungi that are pathogenic on plants experience a special light regime because the host always seeks the optimum light conditions for photosynthesis – and the pathogen has to cope with this environment. When the pathogen lives under the canopy and is indirectly exposed to sunlight, it is confronted with an altered light spectrum enriched for green and far-red light. Botrytis cinerea, the gray mold fungus, is an aggressive plant pathogen mainly infecting the above-ground parts of the plant. As outlined in this review, the Leotiomycete maintains a highly sophisticated light signaling machinery, integrating (near)-UV, blue, green, red and far-red light signals by use of at least eleven potential photoreceptors to trigger a variety of responses, i.e. protection (pigmentation, enzymatic systems), morphogenesis (conidiation, apothecial development), entrainment of a circadian clock, and positive and negative tropism of multicellular (conidiophores, apothecia) and unicellular structures (conidial germ tubes). In that sense, ‘looking through the eyes’ of this plant pathogen will expand our knowledge of fungal photobiology.
Tertiary lymphoid structures in cancer Schumacher, Ton N; Thommen, Daniela S
Science (American Association for the Advancement of Science),
2022-Jan-07, 2022-01-07, 20220107, Letnik:
375, Številka:
6576
Journal Article
Recenzirano
Ectopic lymphoid aggregates, termed tertiary lymphoid structures (TLSs), are formed in numerous cancer types, and, with few exceptions, their presence is associated with superior prognosis and ...response to immunotherapy. In spite of their presumed importance, the triggers that lead to TLS formation in cancer tissue and the contribution of these structures to intratumoral immune responses remain incompletely understood. Here, we discuss the present knowledge on TLSs in cancer, focusing on (i) the drivers of TLS formation, (ii) the function and contribution of TLSs to the antitumor immune response, and (iii) the potential of TLSs as therapeutic targets in human cancers.
Expression of programmed death-ligand 1 (PD-L1) is frequently observed in human cancers. Binding of PD-L1 to its receptor PD-1 on activated T cells inhibits anti-tumor immunity by counteracting ...T cell-activating signals. Antibody-based PD-1-PD-L1 inhibitors can induce durable tumor remissions in patients with diverse advanced cancers, and thus expression of PD-L1 on tumor cells and other cells in the tumor microenviroment is of major clinical relevance. Here we review the roles of the PD-1-PD-L1 axis in cancer, focusing on recent findings on the mechanisms that regulate PD-L1 expression at the transcriptional, posttranscriptional, and protein level. We place this knowledge in the context of observations in the clinic and discuss how it may inform the design of more precise and effective cancer immune checkpoint therapies.
Schumacher et al. review the mechanisms that control PD-L1 expression in cancer and discuss how the growing understanding of the regulation and function of the PD-1-PD-L1 axis can guide more precise and effective immune checkpoint therapies.
Turbulent convection at low Prandtl numbers is in many aspects still terra incognita on the parameter map. One reason for this fact is that laboratory experiments on turbulent convection in this ...parameter regime are notoriously challenging as they require the use of opaque liquid metals. These working fluids prevent the application of typical optical imaging techniques such as particle image velocimetry. Recent experiments by Grannan et al. (J. Fluid Mech., vol. 939, 2022, R1) shed new light on the variety of regimes in liquid metal flows which include rotating convection, magnetoconvection and rotating magnetoconvection next to the classical Rayleigh–Bénard case. More importantly, the authors manage the seamless crossover from one regime into another. They were thus able to study low-Prandtl-number convection at different levels of complexity in a single experimental set-up. Their work provides new insights into the tight connections between characteristic large-scale flow behaviours and the resulting global heat transfer magnitudes. This has implications for convection in planetary cores and stellar convection zones and connected dynamo action.
The tumor protein TP53 gene, encoding the cellular tumor antigen p53, is the single most frequently mutated gene in human cancers. p53 plays a central role in responding to DNA damage and determines ...the outcome of the DNA damage checkpoint response by regulating cell cycle arrest and apoptosis. As a consequence of this function, dysfunctional p53 results in cells that, despite a damaged genome, continue to proliferate thus fueling malignant transformation. New insights have recently been gained into the complexity of the p53 regulation of the DNA damage response (DDR) and how it impacts a wide variety of cellular processes. In addition to cell-autonomous signaling mechanisms, non-cell-autonomous regulatory inputs influence p53 activity, which in turn can have systemic consequences on the organism. New inroads have also been made toward therapeutic targeting of p53 that for a long time has been anticipated.
The tumor protein TP53 is the single most frequently mutated gene in human cancer.p53 is a central regulator of the DNA damage response that impacts cancer and aging.p53 is regulated by non-cell-autonomous mechanisms and exerts systemic consequences.Therapeutic strategies targeting p53 in cancer have recently made significant progress.
Whole-exome sequencing was performed on four patients' tumors before exposure to pembrolizumab and after disease progression following a response to treatment. Acquired mutations involving antigen ...presentation and interferon response were noted.
Durable responses in metastatic cancers have been achieved with a variety of immunotherapies such as interleukin-2, adoptive cell transfer of tumor-infiltrating lymphocytes, antibodies that block cytotoxic T-lymphocyte–associated antigen 4 (CTLA4),
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and antibodies that block programmed death 1 (PD-1).
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However, in a recent study, approximately 25% of patients with melanoma who had had an objective response to PD-1 blockade therapy had disease progression at a median follow-up of 21 months.
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The mechanisms of immune-resistant cancer progression are mostly unknown. Previous studies involving humans examined the loss of beta-2-microglobulin as a mechanism of acquired resistance to several forms of cancer . . .
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