Building Resistance and Resilience: Regeneration Should Not be Left to Chance

Contemporary forest planning has tasked managers with developing goals associated with resistance and resilience. In practice, silviculturists use forest structure and tree species composition to characterize goals and desired future conditions, write prescriptions, and monitor outcomes associated with resistance and resilience. Although rarely discussed in the exploding literature relating to forest resistance and resilience, silvicultural regeneration methods are important and underutilized tools to meet these goals. We propose alternative silvicultural systems for building resistance and resilience to two common large-scale bark beetle disturbance agents in the Intermountain West, United States: mountain pine beetle (Dendroctonus ponderosae Hopkins) and spruce beetle (Dendroctonus rufipennis Kirby). Shelterwood, and shelterwood-with-reserves, silvicultural systems provide the desirable facilitative characteristics of a mature overstory on maintaining advance reproduction and the establishment of new cohorts of desirable tree species. These also allow the timely regeneration of large treatment areas necessary to rapidly promote desired future conditions in the face of inevitable disturbance. When implemented proactively, regeneration treatments allow silviculturists to take advantage of currently existing vegetation for the creation of age class and tree species diversity. In general, these examples illustrate the need for proactive planning for regeneration in response to any disturbance where desired future conditions include particular species. Furthermore, we argue that timely silvicultural interventions that focus on regenerating trees may be a key factor in achieving goals relating to resilience to specific disturbance types. Waiting until after the disturbance has occurred could result in the lost opportunity to establish desired species composition or stand structure—and may well result in a considerable restoration challenge

Landscape-Scale Drivers of Resistance and Resilience to Bark Beetles: A Conceptual Susceptibility Model

Bark beetle (Dendroctonus spp.) outbreaks in the middle latitudes of western North America cause large amounts of tree mortality, outstripping wildfire by an order of magnitude. While temperatures play an important, and direct role in the population dynamics of ectothermic bark beetles, an equally important influence is the nature of the host substrate—the structure and composition of forested communities. For many of the dominant tree species in the western United States, “hazard” indices have been developed for specific bark beetles, which generally include three key variables—host tree size, absolute or relative density of the stand, and percentage of host composition. We provide a conceptual model to apply these three variables across forest ecosystems and bark beetles that shifts the thinking from a species–specific model to a model which focuses on the underlying ecological factors related to bark beetle outbreak susceptibility. We explored the use of our model across multiple scales using the Forest Inventory and Analysis database: Interior West, USA; the states of Colorado and Arizona; and specific national forests within Arizona that are implementing a large-scale restoration effort. We demonstrated that across the Interior West and Colorado, the vast majority of forests have moderate to high susceptibility to bark beetles. Our conceptual model maintains the simplicity of previous “hazard” models but acknowledges the need to consider scale when managing bark beetles. It also shifts the management approach from resistance thinking to the development of “associational resilience”, where the focus is not on any one individual stand or area but the longer-term perspective of forest persistence across the landscape

Real-time optical manipulation of cardiac conduction in intact hearts

Optogenetics has provided new insights in cardiovascular research, leading to new methods for cardiac pacing, resynchronization therapy and cardioversion. Although these interventions have clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies do not take into account cardiac wave dynamics in real time. Here, we developed an all‐optical platform complemented by integrated, newly developed software to monitor and control electrical activity in intact mouse hearts. The system combined a wide‐field mesoscope with a digital projector for optogenetic activation. Cardiac functionality could be manipulated either in free‐run mode with submillisecond temporal resolution or in a closed‐loop fashion: a tailored hardware and software platform allowed real‐time intervention capable of reacting within 2 ms. The methodology was applied to restore normal electrical activity after atrioventricular block, by triggering the ventricle in response to optically mapped atrial activity with appropriate timing. Real‐time intraventricular manipulation of the propagating electrical wavefront was also demonstrated, opening the prospect for real‐time resynchronization therapy and cardiac defibrillation. Furthermore, the closed‐loop approach was applied to simulate a re‐entrant circuit across the ventricle demonstrating the capability of our system to manipulate heart conduction with high versatility even in arrhythmogenic conditions. The development of this innovative optical methodology provides the first proof‐of‐concept that a real‐time optically based stimulation can control cardiac rhythm in normal and abnormal conditions, promising a new approach for the investigation of the (patho)physiology of the heart

Clinical relevance of thymidylate syntetase expression in the signet ring cell histotype component of colorectal carcinoma

Thymidylate Synthase (TS) is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU). The aim of this work was to study TS expression and the proliferation rate in the different histological types of colorectal carcinoma (CRC). 50 patients with CRC were included in this study and evaluated immunohistochemically using the monoclonal antibodies, TS106 and Ki67. 20 tumours were of the intestinal type, 15 cases were signet ring cell carcinoma (SRCCs) and 15 cases were "mixed-type", with at least two different histological components. Intestinal and mucinous histotypes were positive for TS and Ki67, while "signet ring cell" samples were negative or showed only weak and focal positivity for both the TS and Ki67 antibodies. Our results show that signet ring cells (that are also often present in intestinal and mucinous carcinomas), are in the post-mitotic phase of the cell cycle and show a low proliferation index and TS expression. As TS is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU), we can hypothesise that TS expression levels in the different histotypes of CRC could affect the potential responsiveness of these tumours to fluoropyrimidine chemotherapy, with a low efficacy being expected in signet ring cell areas

Label-free electrochemical immunosensor as a reliable point-of-care device for the detection of Interleukin-6 in serum samples from patients with psoriasis

interleukin-6 (IL-6) plays a crucial role in autoimmunity and chronic inflammation. this study aims to develop a low-cost, simple-to-manufacture, and user-friendly label-free electrochemical point-of-care device for the rapid detection of IL-6 in patients with psoriasis. precisely, a sandwich-based format immunosensor was developed using two primary antibodies (mAb-IL6 clone-5 and clone-7) and screen-printed electrodes modified with an inexpensive recycling electrochemical enhancing material, called biochar. mAb-IL6 clone-5 was used as a covalently immobilized capture bioreceptor on modified electrodes, and mAb-IL6 clone-7 was used to recognize the immunocomplex (Anti-IL6 clone-5 and IL-6) and form the sandwich. cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to conduct electrochemical characterization of the layer-by-layer assembly of the immunosensor, while square wave voltammetry (SWV) was used to perform the sensing. the developed immunosensor demonstrated robust analytical performance in buffer solution, with a wide linear range (LR) by varying from 2 to 250 pg/mL, a good limit of detection (LOD) of 0.78 pg/mL and reproducibility (RSD<7%). In addition, a spectrophotometric ELISA kit was employed to validate the results obtained with the label-free device by analyzing twenty-five serum samples from control and patients affected by psoriasis. a strong correlation in terms of pg/mL concentration of IL-6 was found comparing the two methods, with the advantage for our label-free biosensor of an ease use and a quicker detection time. based on IL-6 levels, the proposed immunosensor is a dependable, non-invasive screening device capable of predicting disease onset, progression, and treatment efficacy

Planning intervention using dynamic assessments: A case study

Dynamic assessments (DA) of language have been shown to be a useful addition to the battery of tests used to diagnose language impairments in children, and to evaluate their skills. The current article explores the value of the information gained from a DA in planning intervention for a child with language impairment. A single case study was used to demonstrate the detailed qualitative information that can be derived from a DA procedure, and how that information may be used to elicit greater gains from intervention. The participant was a boy, aged 9, with a previously diagnosed language impairment. He was receiving language therapy regularly in a language resource base attached to his school. The CELF-3(UK) was used to monitor changes in his language, before and after two periods of intervention. The initial baseline phase consisted of regular ongoing language therapy. The second phase of therapy was modified by the speech and language therapist after receiving a report of the child’s performance on the Dynamic Assessment of Sentence Structure (DASS; Hasson et al., 2012), and observations of the child’s metalinguistic and metacognitive awareness. Greater gains observed in the second phase of therapy reflected the good modifiability shown by the child’s performance on the DASS

Trifarotene: a current review and perspectives in dermatology

Retinoids have numerous applications in inflammatory, dyskeratotic, and oncohematology diseases. Retinoids have now reached the fourth generation, progressively reducing toxicity whilst increasing their efficacy. Trifarotene is a new fourth-generation retinoid with a selective action on RAR-γ. In this review, we reported the trials—both concluded and in progress—including the use of trifarotene in dermatological diseases. Studies were identified by searching electronic databases (MEDLINE, EMBASE, PubMed, Cochrane, Trials.gov) from 2012 to today and reference lists of respective articles. Only articles published in English language were included. Randomized trials evaluating trifarotene tolerability, safety, and efficacy in congenital ichthyosis and acne have demonstrated great results and mild side effects, leading to the approval by the FDA of trifarotene for the treatment of lamellar ichthyosis in 2014, and of acne vulgaris in October 2019. No high-quality randomized clinical trials have evaluated the treatment of primary cutaneous lymphomas with trifarotene. Finally, we are hypothesizing future perspectives in the treatment of non-melanoma skin cancers, fungal infections, photoaging, and hand-foot skin reactions with trifarotene

On the estimation of body mass in temnospondyls: a case study using the large-bodied Eryops and Paracyclotosaurus

Temnospondyli are a morphologically varied and ecologically diverse clade of tetrapods that survived for over 200 million years. The body mass of temnospondyls is a key variable in inferring their ecological, physiological and biomechanical attributes. However, estimating the body mass of these extinct creatures has proven difficult because the group has no extant descendants. Here we apply a wide range of body mass estimation techniques developed for tetrapods to the iconic temnospondyls Paracyclotosaurus davidi and Eryops megacephalus. These same methods are also applied to a collection of extant organisms that serve as ecological and morphological analogues. These include the giant salamanders Andrias japonicus and Andrias davidianus, the tiger salamander Ambystoma tigrinum, the California newt Taricha torosa and the saltwater crocodile, Crocodylus porosus. We find that several methods can provide accurate mass estimations across this range of living taxa, suggesting their suitability for estimating the body masses of temnospondyls. Based on this, we estimate the mass of Paracyclotosaurus to have been between 159 and 365 kg, and that of Eryops between 102 and 222 kg. These findings provide a basis for examining body size evolution in this clade across their entire temporal span

Immunomodulatory agents as potential therapeutic or preventive strategies for COVID-19

Currently, the COVID-19 pandemic, caused by the novel SARS-CoV-2 coronavirus, represents the greatest global health threat. Most people infected by the virus present mild to moderate respiratory symptoms and recover with supportive treatments. However, certain susceptible hosts develop an acute respiratory distress syndrome (ARDS), associated with an inflammatory “cytokine storm”, leading to lung damage. Despite the current availability of different COVID-19 vaccines, the new emerging SARS-CoV-2 genetic variants represent a major concern worldwide, due to their increased transmissibility and rapid spread. Indeed, it seems that some mutations or combinations of mutations might confer selective advantages to the virus, such as the ability to evade the host immune responses elicited by COVID-19 vaccines. Several therapeutic approaches have been investigated but, to date, a unique and fully effective therapeutic protocol has not yet been achieved. In addition, steroid-based therapies, aimed to reduce inflammation in patients with severe COVID-19 disease, may increase the risk of opportunistic infections, increasing the hospitalization time and mortality rate of these patients. Hence, there is an unmet need to develop more effective therapeutic options. Here, we discuss the potential use of natural immunomodulators such as Thymosin α1 (Tα1), all-trans retinoic acid (ATRA), and lactoferrin (LF), as adjunctive or preventive treatment of severe COVID-19 disease. These agents are considered to be multifunctional molecules because of their ability to enhance antiviral host immunity and restore the immune balance, depending on the host immune status. Furthermore, they are able to exert a broad-spectrum antimicrobial activity by means of direct interactions with cellular or molecular targets of pathogens or indirectly by increasing the host immune response. Thus, due to the aforementioned properties, these agents might have a great potential in a clinical setting, not only to counteract SARS-CoV-2 infection, but also to prevent opportunistic infections in critically ill COVID-19 patients