Transcriptomic Insights on the Preventive Action of Apple (cv Granny Smith) Skin Wounding on Superficial Scald Development

Superficial scald is a post-harvest chilling storage injury leading to browning of the surface of the susceptible cv Granny Smith apples. Wounding of skins has been reported to play a preventive role on scald development however its underlying molecular factors are unknown. We have artificially wounded the epidermal and sub-epidermal layers of apple skins consistently obtaining the prevention of superficial scald in the surroundings of the wounds during two independent vintages. Time course RNA-Seq analyses of the transcriptional changes in wounded versus unwounded skins revealed that two transcriptional waves occurred. An early wave included genes up-regulated by wounding already after 6 h, highlighting a specific transcriptional rearrangement of genes connected to the biosynthesis and signalling of JA, ethylene and ABA. A later transcriptional wave, occurring after three months of cold storage, included genes up-regulated exclusively in unwounded skins and was prevented from its occurrence in wounded skins. A significant portion of these genes was related to decay of tissues and to the senescence hormones ABA, JA and ethylene. Such changes suggest a wound-inducible reversed hormonal balance during post-harvest storage which may explain the local inhibition of scald in wounded tissues, an aspect that will need further studies for its mechanistic explanation.

Multiscale and extended retrieval of associative memory structures in a cortical model of local-global inhibition balance

Inhibitory neurons take on many forms and functions. How this diversity contributes to memory function is not completely known. Previous formal studies indicate inhibition differentiated by local and global connectivity in associative memory networks functions to rescale the level of retrieval of excitatory assemblies. However, such studies lack biological details such as a distinction between types of neurons (excitatory and inhibitory), unrealistic connection schemas, and non-sparse assemblies. In this study, we present a rate-based cortical model where neurons are distinguished (as excitatory, local inhibitory, or global inhibitory), connected more realistically, and where memory items correspond to sparse excitatory assemblies. We use this model to study how local-global inhibition balance can alter memory retrieval in associative memory structures, including naturalistic and artificial structures. Experimental studies have reported inhibitory neurons and their sub-types uniquely respond to specific stimuli and can form sophisticated, joint excitatory-inhibitory assemblies. Our model suggests such joint assemblies, as well as a distribution and rebalancing of overall inhibition between two inhibitory sub-populations – one connected to excitatory assemblies locally and the other connected globally – can quadruple the range of retrieval across related memories. We identify a possible functional role for local-global inhibitory balance to, in the context of choice or preference of relationships, permit and maintain a broader range of memory items when local inhibition is dominant and conversely consolidate and strengthen a smaller range of memory items when global inhibition is dominant. This model therefore highlights a biologically-plausible and behaviourally-useful function of inhibitory diversity in memory.

Dynamic Hormone Gradients Regulate Wound-Induced de novo Organ Formation in Tomato Hypocotyl Explants

Plants have a remarkable regenerative capacity, which allows them to survive tissue damage after biotic and abiotic stresses. In this study, we use Solanum lycopersicum ‘Micro-Tom’ explants as a model to investigate wound-induced de novo organ formation, as these explants can regenerate the missing structures without the exogenous application of plant hormones. Here, we performed simultaneous targeted profiling of 22 phytohormone-related metabolites during de novo organ formation and found that endogenous hormone levels dynamically changed after root and shoot excision, according to region-specific patterns. Our results indicate that a defined temporal window of high auxin-to-cytokinin accumulation in the basal region of the explants was required for adventitious root formation and that was dependent on a concerted regulation of polar auxin transport through the hypocotyl, of local induction of auxin biosynthesis, and of local inhibition of auxin degradation. In the apical region, though, a minimum of auxin-to-cytokinin ratio is established shortly after wounding both by decreasing active auxin levels and by draining auxin via its basipetal transport and internalization. Cross-validation with transcriptomic data highlighted the main hormonal gradients involved in wound-induced de novo organ formation in tomato hypocotyl explants.

Cholinergic modulation of distinct inhibitory domains in granule cells of the olfactory bulb

Early olfactory processing relies on a large population of inhibitory neurons in the olfactory bulb (OB), the granule cells (GCs). GCs inhibit the OB output neurons, the mitral and tufted cells (M/TCs), shaping their responses to odors both in the spatial and temporal domains, therefore, the activity of GCs is finely tuned by local and centrifugal excitatory and inhibitory inputs. While the circuit substrates underlying regulatory inputs onto GCs are well-established, how they are locally modulated remains unclear. Here, we examine the regulation of GABAergic inhibition onto GCs by acetylcholine, a main neuromodulatory transmitter released in the OB, by basal forebrain (BF) neurons. In acute brain slices from male and female mice, we show that activation of muscarinic acetylcholine receptors (mAChRs) produces opposing effects on local and centrifugal inhibition onto GCs. By using electrophysiology, laser uncaging and optogenetics we show that the kinetics of GABAergic currents in GCs could be correlated with distal and proximal spatial domains from where they originate, along the GC somatodendritic axis. Proximal inhibition from BF afferents, is suppressed by activation of M2/M4-mAChRs. In contrast, distal local inhibition from deep short axon cells (dSACs) is enhanced by activation of M3-mAChRs. Furthermore, we show that the cholinergic enhancement of distal inhibition in GCs reduces the extent of dendrodendritic inhibition in MCs. Interestingly, the excitatory cortical feedback, which also targets the proximal region of GCs, was not modulated by acetylcholine, suggesting that muscarinic activation shifts the synaptic balance towards excitation in GCs. Together, these results suggest that BF cholinergic inputs to the OB fine tune GC-mediated inhibition of M/TCs by differentially modulating the proximal and distal domains of inhibition in GCs.

Hippocampal CA1 pyramidal cells do not receive monosynaptic input from thalamic nucleus reuniens

Midline thalamic nuclei play a critical role in cognitive functions such as memory, decision-making and spatial navigation, by facilitating communication between the many brain regions involved in these processes. One canonical feature of thalamic interactions with the cortex or hippocampus appears to be that the thalamus receives input from, and projects to, excitatory neurons. Thalamic nucleus reuniens (NRe) is located on the midline and is viewed primarily as a relay from prefrontal cortex to hippocampal and entorhinal areas, although these connections are poorly defined at the cellular and synaptic level. Using electrophysiology and monosynaptic circuit-tracing, we found that pyramidal cells in CA1 receive no direct input from NRe. This contrasts starkly with prefrontal cortex, subiculum and entorhinal cortex, and indicates that NRe inputs to CA1 primarily drive local inhibition and not excitation they do in the other regions. The NRe to CA1 projection is thus a unique thalamic projection and as such is raising important questions about the function of NRe-mediated prefrontal control of the hippocampus.

Antibiotic-loaded nonwovens as protection against implant-associated infection

Implant-associated infections still must be considered as a major risk factor and represent a significant threat to the well-being of patients. The detection of such complications is often late, making therapy at this stage difficult. However, the common route of systemic antibiotic prophylaxis can be associated with numerous side effects on the patient or even lead to resistant strains of bacteria. In this context, local antibiotic drug load is a promising way to protect implants against pathogen adhesion and biofilm formation. This work addresses the incorporation of the antibiotic Doxycycline into a biodegradable nonwoven matrix as potential implant coating. While the nonwoven matrix itself displayed already inhibitory effects on Staphylococcus aureus (S. aureus) biofilm formation in vitro, this effect was even more pronounced by the incorporation of Doxycycline. Antibiotic loaded nonwovens display the possibility for local inhibition of biofilm formation. In the shape of an implant coating, this may further help to avoid implantassociated infections. Nevertheless, as pathogens vary in shape and type, further adjustments have to be performed to improve wide-ranging protective effects

The role of von Willebrand factor in the development of systemic infl ammation, coagulopathy and organ dysfunctions

Фактор фон Виллебранда (vWF) является мультимерным гликопротеином, который играет ключевую роль в осуществлении тромбоцитарного и плазменного гемостаза. В последние годы выявлено участие vWF в ангиогенезе, апоптозе нормальных и опухолевых клеток, определена его транспортная роль. Комплекс vWF и фермента ADAMTS-13, который отвечает за его расщепление, имеет существенное значение в развитии воспалительных процессов. Механизмы такого участия vWF различны и включают в себя взаимодействие с микроорганизмами, форменными элементами крови и продуктами их распада, внеклеточными ловушками нейтрофилов, системой комплемента и др. Уникальные свойства молекулы vWF при сепсисе способствуют развитию и прогрессированию коагулопатии. Системное воспаление вносит дополнительный вклад в опосредованное ADAMTS-13 локальное ингибирование расщепления vWF и усугубляет дисбаланс соотношения vWF/ADAMTS-13, тем самым способствуя развитию распространенной внутрисосудистой коагуляции. Образование ультрабольших мультимеров vWF и дефицит ADAMTS-13 выявлены при сепсисе, тяжелом течении COVID-19, черепно-мозговой и сочетанной травме, остром повреждении почек и др. В основе патогенеза возникающей при этом полиорганной недостаточности лежит развитие микроангиопатии и микрососудистых тромбозов. Возможными методами коррекции нарушений в системе vWF/ADAMTS-13 являются применение терапевтического плазмообмена, гепарина, N-ацетилцистеина, рекомбинантного ADAMTS-13, препаратов магния. Von Willebrand factor (vWF) is a multimeric glycoprotein that plays a key role in platelet and plasma hemostasis. In recent years, the involvement of vWF in angiogenesis, apoptosis of normal and tumor cells has been revealed, and its transport role has been determined. The complex of vWF and enzyme ADAMTS-13, which is responsible for its splitting, is essential in the development of inflammatory processes. The mechanisms of vWF participation in inflammatory processes varies and include interaction with microorganisms, blood cells and their degradation products, neutrophil extracellular traps, the complement system, etc. The unique qualities of the vWF contribute to the development and progression of coagulopathy in sepsis. Systemic inflammation enhances local inhibition of vWF cleavage and exacerbates an imbalance in the vWF/ADAMTS-13 ratio, which contributes to the development of intravascular coagulation. The formation of ultralarge vWF (ULvWF) multimers and ADAMTS-13 deficiency were detected in sepsis, severe COVID-19, craniocerebral and concomitant trauma, acute kidney injury, etc. The pathogenesis of the resulting multiple organ failure due to the accumulation of ULvWF is based on the development of microangiopathy and microvascular thrombosis. Possible methods for correcting disorders in the vWF/АDAMTS-13 system are the use of therapeutic plasma exchange, heparin, N-acetylcysteine, recombinant ADAMTS-13, and magnesium preparations.

Positive Feedback Regulation of fzd7 Expression Robustly Shapes Wnt Signaling Range in Early Heart Development

Secreted molecules called morphogens govern tissue patterning in a concentration-dependent manner. However, it is still unclear how reproducible patterning can be achieved with diffusing molecules, especially when patterning differentiation of a thin region. Wnt is a morphogen that organizes cardiac development; especially Wnt6 patterns the cardiogenic mesoderm to induce differentiation of a thin pericardium in Xenopus. It is, however, unclear how Wnt6 can pattern such a thin tissue. In this study, we reveal that a Wnt receptor, frizzled7, is expressed in a Wnt-dependent manner in the prospective heart region, and that this receptor-feedback is essential for shaping a steep gradient of Wnt. In addition, the feedback imparts robustness against fluctuations of Wnt ligand production and allows the system to reach a steady state quickly. We also found a Wnt antagonist sFRP1, which is expressed at the opposite side of Wnt source, accumulates on a novel type of heparan sulfate (HS), N-acetyl-rich HS, which is highly presented in the outer of cardiogenic mesoderm, achieving local inhibition of Wnt signaling by restricting sFRP1 spreading. These two intricate regulatory systems restrict Wnt signaling and ensure reproducible patterning of a thin pericardium tissue.

Feed-forward inhibition fine-tunes response timing in auditory-vocal interactions

The ability to regulate vocal timing is a fundamental aspect of communicative interactions for many species, including conversational speech among humans, yet little is known about the neural circuitry that regulates the input-dependent timing of vocal replies. Exploring this topic in the zebra finch premotor area HVC, we identify feed-forward inhibition as a key regulator of vocal response timing. Based on a spiking network model informed by behavioral and electrophysiological data from communicating zebra finches, we predicted that two different patterns of inhibition regulate vocal-motor responses. In one scenario, the strength of production-related premotor inhibition translates into plasticity in vocal response delays. In the other scenario, fast transient interneuron activity in response to auditory input results in the suppression of call production while a call is heard, thereby reducing acoustic overlap between callers. Extracellular recordings in HVC during the listening phase confirm the presence of auditory-evoked response patterns in putative inhibitory interneurons, along with corresponding signatures of auditory-evoked activity suppression. The proposed model provides a parsimonious framework to explain how auditory-vocal transformations can give rise to vocal turn-taking and highlights multiple roles of local inhibition for behavioral modulation at different time scales.