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Background Purpose Obesity and diabetes are associated with altered gastrointestinal function and with the development of abdominal pain, nausea, diarrhea, and constipation among other symptoms. The enteric nervous system (ENS) regulates gastrointestinal motility. Enteric neuropathies defined as damage or loss of enteric neurons can lead to motility disorders.Here, we review the molecular mechanisms that drive enteric neurodegeneration in diabetes and obesity, including signaling pathways leading to neuronal cell death, oxidative stress, and microbiota alteration. We also highlight potential approaches to treat enteric neuropathies including antioxidant therapy to prevent oxidative stress‐induced damage and the use of stem cells. [ABSTRACT FROM AUTHOR]

This special issue comprises papers presented at the 7th International Entomophagous Insects Conference (IEIC7), in Buenos Aires, Argentina, in 2023. Entomophagous insects, which prey on or parasitize other insects, play a pivotal role in ecosystems and are widely utilized as biocontrol agents. This special issue includes two review articles and nine research papers covering diverse subjects such as ecology, physiology, behavior, genetics, chemical ecology, and biological control, which reflects the diversity of topics presented and discussed during the conference. [ABSTRACT FROM AUTHOR]

The concept of crisis has been widely used to describe European social phenomena which have become acute and unmanageable in recent years. Exceptionality and emergency have become attributes of the political strategies developed to address the economic, social, and environmental unsustainability of industrial farming; the flow of forced migrants; and the COVID‐19 pandemic. This article is based on ethnographic data collected over more than 2 years among immigrant workers and their employers in northern Italy, before and during the spread of the pandemic. By relating the experience of the people involved and analysis of the structural dimensions, I show how the “refugeeization of the agricultural workforce” and the “normalization of precarity” are two interconnected and interdependent processes. My study contributes to the recent scientific debate on the “polycrisis” by highlighting how the agricultural crisis generated a demand for vulnerable migrant labour and this situation was exacerbated by the health crisis. [ABSTRACT FROM AUTHOR]

In mountain forests, tree regeneration is limited by increasingly frequent frosts with increasing elevation. We investigated the effects of exposure to freezing temperature on early life stages of two native trees of different elevational origin in a seasonally dry mountain forest. We hypothesized that the negative effects of freezing exposure on performance of early life stages increases as freezing temperature decreases, and that frost resistance increases in plants of high elevational origin.We collected seeds of two tree species (Kageneckia lanceolata and Lithraea molleoides) from populations located at different elevations and grew seedlings and saplings in a greenhouse. Dry seeds, imbibed seeds and 1‐month‐old seedlings were exposed to seven temperature treatments ranging from 4 °C to −20 °C, while 12‐month‐old saplings were exposed to four temperature treatments from −8 °C to −20 °C. After freezing exposure in a climate chamber, we monitored seed germination and seedling and sapling survival.Germination of K. lanceolata decreased with decreasing temperature only for imbibed seeds from mid‐ and high elevations, whereas germination of L. molleoides slightly increased with decreasing temperature only for imbibed seeds from high elevations. For both species, seedling survival decreased with decreasing temperature. For K. lanceolata, the negative effects of freezing temperatures were weaker as elevational origin of seeds increased, whereas L. molleoides showed the opposite pattern. For both species, saplings only survived at the mildest applied freezing temperature (−8 °C).We conclude that effects of climatic variation associated with elevation depend on the study species and life stage. The observed patterns could be caused by maternal effects, which are absent at the sapling stage. Moreover, temperatures below −8 °C can limit recruitment since partial mortality of seedlings and saplings occurred at such values. [ABSTRACT FROM AUTHOR]

As the introduction of antiretroviral therapy (ART) during primary HIV‐1 infection (PHI) could restrict the establishment of HIV reservoirs, we aimed to assess the effect of three different ART regimens on HIV‐DNA load in people living with HIV (PLWH), who started ART in PHI. Randomized, open‐label, multicentric study, including subjects in PHI (defined as an incomplete HIV‐1 Western blot and detectable plasma HIV‐RNA) in the Italian Network of Acute HIV Infection cohort. Participants were randomly assigned (10:10:8) to a fixed‐dose combination of tenofovir alafenamide fumarate (TAF) 10 mg plus emtricitabine (FTC) 200 mg, darunavir 800 mg, and cobicistat 150 mg once daily (group A), or TAF 25 mg plus FTC 200 mg, dolutegravir 50 mg once daily (group B), or an intensified four‐drug regimen (TAF 10 mg plus FTC 200 mg, dolutegravir 50 mg, darunavir 800 mg, and cobicistat 150 mg once daily) (group C). The primary endpoint was the decrease of HIV‐DNA copies/106 peripheral blood mononuclear cells (PBMCs) at weeks (W) 12 and 48. Secondary endpoints were increased in CD4+ cells and in CD4+/CD8+ ratio and percentage of PLWH reaching undetectable HIV‐RNA. HIV‐DNA was quantified by Droplet Digital PCR (Biorad QX100) and normalized to RPP30 reference gene. This study was registered in ClinicalTrials.gov (number NCT04225325). Among 78 participants enrolled, 30 were randomized to group 1, 28 to group 2, and 20 to group 3. At baseline, median CD4+ count was 658/µL (476–790), HIV‐RNA 5.37 (4.38, 6.12) log10 copies/mL, without statistical difference in their change among groups at weeks 12 and 48 (p = 0.432 and 0.234, respectively). The trial was prematurely discontinued for slow accrual and for COVID‐19 pandemic‐associated restrictions. In the per‐protocol analysis, PLWH (n = 72) with undetectable viral load was 54.3% at W12 and 86.4% at W48. Interestingly, the CD4/CD8 ratio progressively increased over time, up to normalization in almost half of the cohort by week 48, despite a deflection in group 3; no difference was observed by the Fiebig stage (I–III vs. IV–VI). HIV‐DNA decreased from 4.46 (4.08, 4.81) log10 copies/106 PBMCs to 4.22 (3.79, 4.49) at week 12, and 3.87 (3.46, 4.34) at week 48, without difference among groups. At multivariable analysis, HIV‐DNA delta at W48 was associated only with the increase of CD4+ count by 100 cells/mm3 but not with the Fiebig stage, the CD4+/CD8+ ratio, and treatment arm, despite a higher decrease in group 3. Six adverse events were recorded during our study, which did not cause any withdrawal from the study. We observed a decrease in HIV‐DNA from baseline to W48 in PLWH treated during PHI, associated with an increase in CD4+ count, unrelated to the treatment arm. [ABSTRACT FROM AUTHOR]

Monitoring vegetation trends against objective baselines is fundamental to quantify the impacts of global change on plant biodiversity. Vegetation plot time series are a gold standard in vegetation monitoring, but such data are missing for many regions. Southern Patagonia is an example of a region strongly impacted by climate change but lacking time series data. Monitoring in this region could benefit from a comparison with vegetation survey data gathered between 1975 and 1979, as part of the multidisciplinary research program "Transecta botánica de la Patagonia austral" (hereafter Transecta). Published in 1985, it contains data on 668 vegetation plots, which were so far inaccessible to most researchers: Transecta has never been reprinted, nor fully digitized, and can only be found in specialized libraries. Here, we created a reproducible workflow, documenting how vegetation plot data from historical sources can be extracted and harmonized. The resulting open‐access database we created fills a major regional gap and provides a needed baseline to assess the impacts of global change on southern Patagonia vegetation. By making these data available, we hope to inspire a new generation of vegetation scientists to resurvey the area and continue the legacy of the pioneer researchers who compiled Transecta. [ABSTRACT FROM AUTHOR]

Patient N. 4 had moderate COVID-19 disease four months before cell therapy, requiring hospital admission and oxygen support because of interstitial pneumonia. Severe COVID-19 disease and COVID-19-related mortality were registered in 39% and 41% of patients, respectively. Starting from February 2021, the distribution of monoclonal antibody (MoA) casirivimab/imdevimab was authorized in Italy for the treatment of mild to moderate COVID-19 disease in patients at high risk for developing severe illness. COVID-19 infection has affected hematologic patients more severely than general population, probably due to underlying impaired immunity response, active chemotherapy and immunosuppressive treatment. [Extracted from the article]

In a context where states increasingly complement their physical presence with digital means, the classic idea of infrastructural state power needs reconsideration. The COVID‐19 pandemic represents an unparalleled opportunity to that end, given the uniformity of one type of digital infrastructural intervention—the offer of contact tracing apps‐ and its highly varying performance across geographies. Against this backdrop, the article seeks to expand traditional discussions on state infrastructural power by testing a series of propositions on the explanatory factors behind tracing apps' emergence and adoption rates. The findings stemming from a pool of 150 countries show no straightforward connection between traditional and digital forms of infrastructural power. They also point at the primacy of governmental trust over financial, institutional, and technological factors—including privacy standards—when explaining high adoption, suggesting that the relational aspect of infrastructural power acquires a proportionally greater weight in the digital era. [ABSTRACT FROM AUTHOR]

Liquid metal catalysts have recently attracted attention for synthesizing high‐quality 2D materials facilitated via the catalysts' perfectly smooth surface. However, the microscopic catalytic processes occurring at the surface are still largely unclear because liquid metals escape the accessibility of traditional experimental and computational surface science approaches. Hence, numerous controversies are found regarding different applications, with graphene (Gr) growth on liquid copper (Cu) as a prominent prototype. In this work, novel in situ and in silico techniques are employed to achieve an atomic‐level characterization of the graphene adsorption height above liquid Cu, reaching quantitative agreement within 0.1 Å between experiment and theory. The results are obtained via in situ synchrotron X‐ray reflectivity (XRR) measurements over wide‐range q‐vectors and large‐scale molecular dynamics simulations based on efficient machine‐learning (ML) potentials trained to first‐principles density functional theory (DFT) data. The computational insight is demonstrated to be robust against inherent DFT errors and reveals the nature of graphene binding to be highly comparable at liquid Cu and solid Cu(111). Transporting the predictive first‐principles quality via ML potentials to the scales required for liquid metal catalysis thus provides a powerful approach to reach microscopic understanding, analogous to the established computational approaches for catalysis at solid surfaces. [ABSTRACT FROM AUTHOR]

The transactivation response‐DNA binding protein of 43 kDa (TDP‐43) is an aggregation‐prone nucleic acid‐binding protein linked to the etiology of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). These conditions feature the accumulation of insoluble TDP‐43 aggregates in the neuronal cytoplasm that lead to cell death. The dynamics between cytoplasmic and nuclear TDP‐43 are altered in the disease state where TDP‐43 mislocalizes to the cytoplasm, disrupting Nuclear Pore Complexes (NPCs), and ultimately forming large fibrils stabilized by the C‐terminal prion‐like domain. Here, we review three emerging and poorly understood aspects of TDP‐43 biology linked to its aggregation. First, how post‐translational modifications in the proximity of TDP‐43 N‐terminal domain (NTD) promote aggregation. Second, how TDP‐43 engages FG‐nucleoporins in the NPC, disrupting the pore permeability and function. Third, how the importin α/β heterodimer prevents TDP‐43 aggregation, serving both as a nuclear import transporter and a cytoplasmic chaperone. [ABSTRACT FROM AUTHOR]

We establish Moser–Trudinger‐type inequalities in the presence of a logarithmic convolution potential when the domain is a ball or the entire space R2$\mathbb {R}^2$. Moreover, we characterize critical nonlinear growth rates for these inequalities to hold and for the existence of corresponding extremal functions. In addition, we show that extremal functions satisfy corresponding Euler–Lagrange equations, and we derive general symmetry and uniqueness results for solutions of these equations. [ABSTRACT FROM AUTHOR]

Trans women face multiple social, economic and health inequalities and the impact of gender oppression and violence is even more profoundly experienced by trans women sex workers, although in culturally specific ways. This paper presents a pilot study conducted to explore and engage with the context of trans women sex workers in Lido Tre Archi, Italy. In line with the community psychology values of social justice, social change and participation, we outline our engagement process and key challenges observed when attempting action research with such a highly marginalised group. Data were collected in the form of ethnographic notes from informal consultations with different stakeholders and participant observations, and of documents (newspaper articles, picture captions) and were analysed using thematic analysis. Findings are organised in three themes relating to the social, policy and physical context in Lido Tre Archi demonstrating evidence of the contextual challenges and how they intertwine to generate a spiral of marginalisation and social exclusion for the participants. We take a collaborative and reflexive stance in our work and conclude with recommended steps and potential limitations to initiate an action research project. [ABSTRACT FROM AUTHOR]

The article informs about unusual right bundle branch origin ventricular arrhythmias, and electroanatomical insights for successful catheter ablation. Topics include Right bundle branch ventricular arrhythmias (RBB-VA) are rare arrhythmias with various clinical presentations and suboptimal responses to medical therapy; and systematic analysis of electrophysiologic properties, conduction block, and catheter ablation of this rare arrhythmia is incomplete.

Bicontinuous jammed emulsions (known as bijels) are Pickering emulsions where oil and water are both continuous phases. These interconnected structures, stabilized by colloidal nanoparticles at the oil–water interface, have been used in a wide range of applications. Among these, catalysis and encapsulation of solutes has showed promising potential, but the low mechanical properties of the systems limit their use. Here it is proposed that the use of a hydrophobic monomer able to polymerize in bulk and form a biphasic porous structure with polymer and water as immiscible phases. The final system is stabilized by colloidal nanoparticles made of hydroxyapatite, and the system's ability to release both hydrophilic and hydrophobic drugs has been demonstrated. The strategy has been proven to be highly versatile and may be tuned with a diversity of monomers and nanoparticles to satisfy specific industrial and medical needs. [ABSTRACT FROM AUTHOR]

Highlights: Zinc ascorbate could prevent and treat Covid‐19 by raising antiviral resistance to SARS‐CoV‐2 virus via increase of intracellular zinc concentration as a zinc ionophore more than other salts of zinc or zinc with vitamin C. Tests in vitro and clinical trials for Covid‐19 prevention and treatment with zinc ascorbate are strongly recommended and should start as soon as possible. Potential advantages of zinc ascorbate supplementation over vaccines and drugs are also discussed, with supplementation suggestions. [ABSTRACT FROM AUTHOR]

The repertoire of natural products offers tremendous opportunities for chemical biology and drug discovery. Natural product‐inspired synthetic molecules represent an ecologically and economically sustainable alternative to the direct utilization of natural products. De novo design with machine intelligence bridges the gap between the worlds of bioactive natural products and synthetic molecules. On employing the compound Marinopyrrole A from marine Streptomyces as a design template, the algorithm constructs innovative small molecules that can be synthesized in three steps, following the computationally suggested synthesis route. Computational activity prediction reveals cyclooxygenase (COX) as a putative target of both Marinopyrrole A and the de novo designs. The molecular designs are experimentally confirmed as selective COX‐1 inhibitors with nanomolar potency. X‐ray structure analysis reveals the binding of the most selective compound to COX‐1. This molecular design approach provides a blueprint for natural product‐inspired hit and lead identification for drug discovery with machine intelligence. [ABSTRACT FROM AUTHOR]

Integrins are extracellular matrix receptors that mediate biochemical and mechanical bi‐directional signals between the extracellular and intracellular environment of a cell thanks to allosteric conformational changes. In the brain, they are found in both neurons and glial cells, where they play essential roles in several aspects of brain development and function, such as cell migration, axon guidance, synaptogenesis, synaptic plasticity and neuro‐inflammation. Although there are many successful examples of how regulating integrin adhesion and signaling can be used for therapeutic purposes, for example for halting tumor progression, this is not the case for the brain, where the growing evidence of the importance of integrins for brain pathophysiology has not translated yet into medical applications. Here, we review recent literature showing how alterations in integrin structure, expression and signaling may be involved in the etiology of autism spectrum disorder, epilepsy, schizophrenia, addiction, depression and Alzheimer's disease. We focus on common mechanisms and recurrent signaling pathways, trying to bridge studies on the genetics and molecular structure of integrins with those on synaptic physiology and brain pathology. Further, we discuss integrin‐targeting strategies and their potential benefits for therapeutic purposes in neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

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Invasive stink bugs (Hemiptera: Pentatomidae) are responsible for high economic losses to agriculture on a global scale. The most important species, dating from recent to old invasions, include Bagrada hilaris (Burmeister), Halyomorpha halys (Stål), Piezodorus guildinii (Westwood), Nezara viridula (L.), and Murgantia histrionica (Hahn). Bagrada hilaris, H. halys, and N. viridula are now almost globally distributed. Biological control of these pests faces a complex set of challenges that must be addressed to maintain pest populations below the economic injury level. Several case studies of classical and conservation biological control of invasive stink bugs are reported here. The most common parasitoids in their geographical area of origin are egg parasitoids (Hymenoptera: Scelionidae, Encyrtidae, and Eupelmidae). Additionally, native parasitoids of adult stink bugs (Diptera: Tachinidae) have in some cases adapted to the novel hosts in the invaded area and native predators are known to prey on the various instars. Improving the efficacy of biocontrol agents is possible through conservation biological control techniques and exploitation of their chemical ecology. Moreover, integration of biological control with other techniques, such as behavioural manipulation of adult stink bugs and plant resistance, may be a sustainable pest control method within organic farming and integrated pest management programs. However, additional field studies are needed to verify the efficacy of these novel methods and transfer them from research to application. [ABSTRACT FROM AUTHOR]

While olfactory dysfunction associated with coronavirus disease 2019 (COVID-19) has attracted considerable interest, few studies have tracked outcomes at serial time points or beyond 2 weeks. Furthermore, data are conflicting regarding whether COVID-19 severity correlates with degree of olfactory dysfunction. This prospective case-control study analyzed prevalence and severity of subjective loss of smell in outpatients (n = 23) and inpatients (n = 20) with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vs healthy controls (n = 25). Olfactory dysfunction was reported more commonly in COVID-19 patients than in healthy controls (P <.001), and outpatients paradoxically reported loss of smell more commonly than inpatients (P =.02). Headaches were present in 52% of patients with olfactory dysfunction. Anosmia or hyposmia persisted beyond 5 days but most of the patients recovered by 30 days, suggesting favorable prognosis for olfaction. Differences between inpatients and outpatients are potentially reflective of timeline of olfactory symptoms and contextual factors, underscoring the importance of corroborative objective testing, coupled with careful tracking of temporal relationships. [ABSTRACT FROM AUTHOR]

Key points: Heart failure (HF), the leading cause of death in developed countries, occurs in the setting of reduced (HFrEF) or preserved (HFpEF) ejection fraction. Unlike HFrEF, there are no effective treatments for HFpEF, which accounts for ∼50% of heart failure.Abnormal intracellular calcium dynamics in cardiomyocytes have major implications for contractility and rhythm, but compared to HFrEF, very little is known about calcium cycling in HFpEF.We used rat models of HFpEF and HFrEF to reveal distinct differences in intracellular calcium regulation and excitation‐contraction (EC) coupling.While HFrEF is characterized by defective EC coupling at baseline, HFpEF exhibits enhanced coupling fidelity, further aggravated by a reduction in β‐adrenergic sensitivity.These differences in EC coupling and β‐adrenergic sensitivity may help explain why therapies that work in HFrEF are ineffective in HFpEF. Heart failure with reduced or preserved ejection fraction (respectively, HFrEF and HFpEF) is the leading cause of death in developed countries. Although numerous therapies improve outcomes in HFrEF, there are no effective treatments for HFpEF. We studied phenotypically verified rat models of HFrEF and HFpEF to compare excitation‐contraction (EC) coupling and protein expression in these two forms of heart failure. Dahl salt‐sensitive rats were fed a high‐salt diet (8% NaCl) from 7 weeks of age to induce HFpEF. Impaired diastolic relaxation and preserved ejection fraction were confirmed in each animal echocardiographically, and clinical signs of heart failure were documented. To generate HFrEF, Sprague‐Dawley (SD) rats underwent permanent left anterior descending coronary artery ligation which, 8–10 weeks later, led to systolic dysfunction (verified echocardiographically) and clinical signs of heart failure. Calcium (Ca2+) transients were measured in isolated cardiomyocytes under field stimulation or patch clamp. Ultra‐high‐speed laser scanning confocal imaging captured Ca2+ sparks evoked by voltage steps. Western blotting and PCR were used to assay changes in EC coupling protein and RNA expression. Cardiomyocytes from rats with HFrEF exhibited impaired EC coupling, including decreased Ca2+ transient (CaT) amplitude and defective couplon recruitment, associated with transverse (t)‐tubule disruption. In stark contrast, HFpEF cardiomyocytes showed saturated EC coupling (increased ICa, high probability of couplon recruitment with greater Ca2+ release synchrony, increased CaT) and preserved t‐tubule integrity. β‐Adrenergic stimulation of HFpEF myocytes with isoprenaline (isoproterenol) failed to elicit robust increases in ICa or CaT and relaxation kinetics. Fundamental differences in EC coupling distinguish HFrEF from HFpEF. Key points: Heart failure (HF), the leading cause of death in developed countries, occurs in the setting of reduced (HFrEF) or preserved (HFpEF) ejection fraction. Unlike HFrEF, there are no effective treatments for HFpEF, which accounts for ∼50% of heart failure.Abnormal intracellular calcium dynamics in cardiomyocytes have major implications for contractility and rhythm, but compared to HFrEF, very little is known about calcium cycling in HFpEF.We used rat models of HFpEF and HFrEF to reveal distinct differences in intracellular calcium regulation and excitation‐contraction (EC) coupling.While HFrEF is characterized by defective EC coupling at baseline, HFpEF exhibits enhanced coupling fidelity, further aggravated by a reduction in β‐adrenergic sensitivity.These differences in EC coupling and β‐adrenergic sensitivity may help explain why therapies that work in HFrEF are ineffective in HFpEF. [ABSTRACT FROM AUTHOR]

Summary: A low count of CD4+ and CD8+ lymphocytes is a hallmark laboratory finding in the coronavirus disease 2019 (COVID‐19). Using flow cytometry, we observed significantly higher CD95 (Fas) and PD‐1 expression on both CD4+ T and CD8+ T cells in 42 COVID‐19 patients when compared to controls. Higher CD95 expression in CD4+ cells correlated with lower CD4+ counts. A higher expression of CD95 in CD4+ and CD8+ lymphocytes correlated with a lower percentage of naive events. Our results might suggest a shift to antigen‐activated T cells, expressing molecules increasing their propensity to apoptosis and exhaustion during COVID‐19 infection. [ABSTRACT FROM AUTHOR]

The genome‐packaging motor of tailed bacteriophages and herpesviruses is a multisubunit protein complex formed by several copies of a large (TerL) and a small (TerS) terminase subunit. The motor assembles transiently at the portal protein vertex of an empty precursor capsid to power the energy‐dependent packaging of viral DNA. Both the ATPase and nuclease activities associated with genome packaging reside in TerL. Structural studies of TerL from bacteriophage P22 have been hindered by the conformational flexibility of this enzyme and its susceptibility to proteolysis. Here, an unbiased, synthetic phage‐display Fab library was screened and a panel of high‐affinity Fabs against P22 TerL were identified. This led to the discovery of a recombinant antibody fragment, Fab4, that binds a 33‐amino‐acid α‐helical hairpin at the N‐terminus of TerL with an equilibrium dissociation constant Kd of 71.5 nM. A 1.51 Å resolution crystal structure of Fab4 bound to the TerL epitope (TLE) together with a 1.15 Å resolution crystal structure of the unliganded Fab4, which is the highest resolution ever achieved for a Fab, elucidate the principles governing the recognition of this novel helical epitope. TLE adopts two different conformations in the asymmetric unit and buries as much as 1250 Å2 of solvent‐accessible surface in Fab4. TLE recognition is primarily mediated by conformational changes in the third complementarity‐determining region of the Fab4 heavy chain (CDR H3) that take place upon epitope binding. It is demonstrated that TLE can be introduced genetically at the N‐terminus of a target protein, where it retains high‐affinity binding to Fab4. [ABSTRACT FROM AUTHOR]

Agencification has been pursued globally under the promise of increasing public administration performance. In spite of ample theoretical arguments, the empirical evidence on the causal link between agencification and performance remains scarce and methodologically contested. We contribute to this debate by empirically testing the impacts of agencification across Germany, Spain, and the United Kingdom on value‐for‐money, competitiveness, and timeliness during the period 2006–2016. We use unique administrative datasets, enabling objective and granular measurements of reforms and their effects, employing quasi‐experimental methods. Findings suggest heterogeneous effects both across countries and outcomes. On average, value‐for‐money improves by 2.8% or 1.7 billion EUR over a decade, while outputs and processes change only marginally. Recently agencified organizations barely improve their performance, while older agencies achieve substantial improvements. The three countries' heterogeneous administrative contexts play a critical role as mediating factors, with the biggest changes occurring in higher new public management take‐up countries. [ABSTRACT FROM AUTHOR]

Bioresorbable pins are experiencing a growing interest and a likewise increasing use in orthopedic surgery for bone fixation. Indeed, such devices are naturally degraded by the human body and a subsequent surgery for their removal is not needed. However, bioresorption has a remarkable side effect on the performance of the devices, since mechanical properties decay over time. This aspect is essential for bone healing. In the first 60 days, the pin must bear continuous mechanical stress while preventing torsional slip of bone fragments. Although torsional support can be improved with suitable pin section design, degradation kinetics and the consequent loss in mechanical stability are slowed down while using high molecular weight polymers, whose slow bioresorption increases recovery time and negatively affects patient care. Herein, a bioresorbable pin of new conception, in terms of cross‐sectional shape and material formulation, is presented. Both section and polymer design are optimized through comprehensive mathematical modeling, which synergistically combines degradation and mechanical loads. As a result of the model, bioresorption time is minimized, whereas adequate mechanical resistance is ensured for the first 60 days. The most promising device is then injection molded, sterilized, mechanically tested, and successfully evaluated ex vivo in human femoral heads. [ABSTRACT FROM AUTHOR]

The reactivity of the dinuclear complex dicarbonyl[η4‐3,4‐bis(4‐methoxyphenyl)‐2,5‐diphenylcyclopenta‐2,4‐dienone] (2) with imidazolium salts has been studied using a library of variously functionalized imidazolium salts, and leading to a class of ruthenium anionic complexes of the type [dicarbonyl{η4‐3,4‐bis(4‐methoxyphenyl)‐2,5‐diphenylcyclopenta‐2,4‐dienone} (halide)Ru][1,3‐disubsittuted‐imidazolium] (4) in the form of ion pair with imidazolium. The reaction is clean, general and quantitative and the complexes formed are stable to air and moisture both in the solid state and in solution. The ionic complexes 4 show affinity for ionic liquids and represent stable precursors of a catalytic active species, likely similar to those generated from Shvo catalyst, a well‐established homogeneous bifunctional catalyst for hydrogen transfer. Our approach allows the use of green ionic liquids (IL) as solvents, providing better control of catalytic reactions involving 4, and easier catalyst recycle. IL‐supported ionic pair catalysts exhibit interesting catalytic activity (up to > 99 % of conversion) in the transfer hydrogenation of a model compound such as 4‐fluoroacetophenone. The IL‐supported redox catalysts can be also recycled exploiting the biphasic nature of the system. The synthetic method here discussed represents a novelty within the field of IL‐supportation and is potentially useful for the heterogenization of the catalysts. [ABSTRACT FROM AUTHOR]

Objectives: Two‐drug antiretroviral regimens based on lamivudine (3TC) plus either a protease inhibitor (PI) or dolutegravir (DTG) are becoming increasingly popular in switch strategies. Our goal was to derive a predictive score for virological failure (VF). Methods: We retrospectively analysed data for a cohort of 587 virologically suppressed (HIV RNA < 37 HIV‐1 RNA copies/mL), adult (≥ 18 years old) patients starting lamivudine plus either a boosted PI or dolutegravir. Predictors of VF (defined as a single HIV RNA measurement ≥ 1000 copies/mL or two consecutive HIV RNA measurements ≥ 50 copies/mL) were identified using a multivariate Cox regression model. A 'weighted' score was assigned to each variable associated with VF; the discriminative power of the score obtained was expressed as the area under the receiver‐operator characteristic curve (ROC‐AUC). Results: During a median 2 years of follow‐up time, 35 VFs occurred; predictors of VF were baseline residual HIV RNA between 20 and 36 copies/mL, African ethnicity, ≥ 10 therapeutic lines, the presence of at least one resistance‐associated mutation (RAM) for resistance to current drugs (excluding M184V), a non‐B viral subtype and a baseline CD4 count < 200 cells/μL. A score of 2 was assigned to non‐B viral subtype, 3 to residual viraemia ≥ 20 copies/mL, ≥ 10 previous therapeutic lines and African ethnicity, 4 to baseline CD4 count < 200 cells/μL, and 7 to the presence of at least one RAM (excluding M184V). The ROC‐AUC was 0.67 (95% confidence interval 0.57–0.77). Conclusions: The presence of at least one RAM, higher residual viraemia and African ethnicity were among the major predictors of VF in our cohort. Studies with larger sample sizes are warranted to improve the predictive value of the derived score. [ABSTRACT FROM AUTHOR]

Background: Esophageal injury is related to a reduction in luminal esophageal temperature (LET) in second‐generation cryoballoon (CB) ablation; however, methods to prevent these reductions in temperature have not been well characterized. Methods: Esophageal temperature was continuously monitored using a LET probe in patients undergoing pulmonary vein (PV) isolation using the second‐generation CB. A rotational maneuver of the CB was performed if the initial ablation resulted in a decrease of more than 4℃ in LET. The refrigerant injector near the distal CB pole was used as a fluoroscopic marker to measure the nearest distance between the CB and the LET probe. Results: A total of 52 consecutive patients were enrolled in this study. The rotation was applied in 19 patients and 20 PVs (seven left superior pulmonary veins [LSPVs], seven left inferior PVs [LIPVs], and six right inferior PVs [RIPVs]) with a reduction in LET of more than 4℃ during freezing. The nadir temperature of CB applications was similar before and after CB rotation in all PVs. There was significant difference in the minimum LET before and after rotation during freezing in LSPVs (28.4 ± 3.7 vs 32.4 ± 2.3℃, P = .02), LIPVs (28.4 ± 1.4 vs 32.6 ± 2.7, P = .01) and RIPVs (26.1 ± 4.3 vs 34.0 ± 1.3℃, P = .002). The differences in mean balloon to LET distance were measured for all veins before and after rotation; LSPV (right anterior oblique [RAO], 11.0 ± 1.7 vs 13.8 ± 4.5 mm, P = .05); LIPV (RAO, 10.7 ± 4.3 vs 14.6 ± 6.1 mm, P = .03); RIPV (LAO, 11.8 ± 5.5 vs 14.2 ± 5.7 mm, P = .01). Conclusions: CB rotational maneuvers during ablation can prevent significant reduction in LET and may prevent esophageal injury during the procedure. [ABSTRACT FROM AUTHOR]

Background: One mechanism underlying the development of alcoholic liver disease is overactivation of the innate immune response. Recent investigations indicate that the lysosomal pathway of autophagy down‐regulates the inflammatory state of hepatic macrophages, suggesting that macrophage autophagy may regulate innate immunity in alcoholic liver disease. The function of macrophage autophagy in the development of alcoholic liver disease was examined in studies employing mice with a myeloid‐specific decrease in autophagy. Methods: Littermate control and Atg5Δmye mice lacking Atg5‐dependent myeloid autophagy were administered a Lieber–DeCarli control (CD) or ethanol diet (ED) alone or together with lipopolysaccharide (LPS) and examined for the degree of liver injury and inflammation. Results: Knockout mice with decreased macrophage autophagy had equivalent steatosis but increased mortality and liver injury from ED alone. Increased liver injury and hepatocyte death also occurred in Atg5Δmye mice administered ED and LPS in association with systemic inflammation as indicated by elevated serum levels of proinflammatory cytokines. Hepatic macrophage and neutrophil infiltration were unaffected by decreased autophagy, but levels of proinflammatory cytokine gene induction were significantly increased in the livers but not adipose tissue of knockout mice treated with ED and LPS. Inflammasome activation was increased in ED/LPS‐treated knockout mice resulting in elevated interleukin (IL)‐1β production. Increased IL‐1β promoted alcoholic liver disease as liver injury was decreased by the administration of an IL‐1 receptor antagonist. Conclusions: Macrophage autophagy functions to prevent liver injury from alcohol. This protection is mediated in part by down‐regulation of inflammasome‐dependent and inflammasome‐independent hepatic inflammation. Therapies to increase autophagy may be effective in this disease through anti‐inflammatory effects on macrophages. Liver injury and inflammation in alcoholic liver disease are associated with overactivation of the innate immune system. Among the cellular mechanisms that control inflammation, autophagy regulates the hepatic immune response in a number of liver diseases. In this study the protective role of macrophage autophagy was examined in a mouse model of alcoholic liver disease. Macrophage autophagy downregulates hepatic inflammation and liver injury, suggesting that therapies directed to increase macrophage autophagy might be beneficial in the treatment of alcoholic liver disease. [ABSTRACT FROM AUTHOR]

Abstract: Rivers originating in the granitic highlands of seasonally dry central Argentina provide water to 2 million people. These highlands comprise a complex landscape where a matrix of outcropping rock hosts vegetated patches that vary in response to long‐term grazing and fire. We characterized water storage dynamics across 20 sites representing 6 vegetation‐soil conditions with similar mid‐upslope positions in the landscape. We measured temporal and spatial variability of water inputs (rain and fog) and water stored at the unsaturated and saturated zones. We found that rainfall was highly seasonal, but fog occurred year‐round, likely representing an extra water source in areas with complex vegetation structure. Moreover, fog seems to regulate evapotranspiration/topsoil water dynamics. Water was stored in the saturated zone only during the rainy season. Piezometric response to rainfall was rapid but transient (dropping an average 15 cm/day), possibly buffering peak stormflows, reducing sediment yield, and delivering subsurface water downslope for potential storing throughout the year. Spatially, a reduction in soil depth (from 100 up to 9 cm) and vegetation structure (from woodlands to stonelands), with a degradation of topsoil conditions for infiltration were accompanied by a decline in water storage at the unsaturated (from 32% up to 14%) and saturated (from 46.3 up to 0 cm) zones. Taken together, our results support the infiltration trade‐off hypothesis, which states that vegetation structure benefits fog interception, soil properties that enhance water infiltration, subsurface flow paths, and storage. Long‐term disturbances have likely triggered a degradation of the hydrological function of seasonal highlands in central Argentina. [ABSTRACT FROM AUTHOR]

In this case study, the body of a 45-year-old man was exhumed after 1 year at the request of the public prosecutor to assess whether the death was caused by drug consumption. Toxicological analyses were performed on several matrices, including liver, kidney, and the alternative matrices hair and teeth. The systematic toxicological analysis (STA), which consisted of basic and acid liquid/liquid extraction and gas chromatography-mass spectrometry (GC-MS) analysis, showed the presence of opiates in each of the matrices analyzed. Subsequently, to confirm and quantify the presence of opioids, samples of each of the matrices were subjected to solid-phase extraction and specific GC-MS analysis. The case presented demonstrates the possibility of drug detection in an exhumed body that has been buried for 1 year, despite the problems of quantitative interpretation of the data, and that toxicological results could be useful along with other forensic evidence. [ABSTRACT FROM AUTHOR]

Abstract: A selection of cobalt(I) and cobalt(II) pincer type complexes with different substitution patterns was tested in the catalytic reduction of carboxylic acid esters to alcohols. The cobalt pincer type complex 4 is suitable for the hydrogenation of aromatic as well as aliphatic and cyclic esters. Mechanistic investigation indicated a metal ligand cooperated reaction pathway. [ABSTRACT FROM AUTHOR]

Abstract: Reliable control of pore size distribution in porous materials is a key feature for addressing specific applications. The reactive gelation process represents a robust and efficient method to obtain mechanically stable monoliths with tunable pore size distribution. Primary polymer nanoparticles are destabilized and aggregated in a controlled way, forming a percolating gel. Afterward, this structure is hardened by a postpolymerization, carried out through heating. Different parameters play a major role in determining the final morphology of the monolith. In this work, the effect of primary particle architecture (i.e., core‐to‐shell ratio) and initial solid content of the latex is investigated, using two different sizes of nanoparticles. Actually, the first parameter affects the pores in the small range (0.01–1 µm) whereas the latter those in the larger one (1 µm to several micrometers), independently of the primary particle size. As a result, monoliths with very well‐defined pore size distributions are obtained. [ABSTRACT FROM AUTHOR]

Questions Most vegetation descriptions tacitly assume that floristic composition and physiognomy are tightly linked. However, the two vegetation properties may not respond in a similar way to environmental and disturbance gradients, leading to uninformed management planning and difficulties when attempting to restore degraded ecosystems. In this context, we addressed two main questions: (1) how close are relations between floristic and physiognomic types as defined by numerical vegetation classification in mountain ecosystems; and (2) how are floristic and physiognomic types distributed along the elevation gradient? Location Central mountains of Argentina, between 500 and 1700 m a.s.l. Methods We selected 437 sites where we performed complete floristic and physiognomic relevés. We classified eight physiognomic and eight floristic types. We tested the relationship between the two classifications through a chi square analysis. We tested the association between elevation and each physiognomic and floristic type with random permutations. Results In general, floristic types were significantly and positively associated with more than one physiognomic type and vice versa. Physiognomic and floristic types responded differently to the elevation gradient. Floristic types were restricted to different sections of the gradient, although having large overlap among them. In contrast, seven out of the eight physiognomic types did not show elevation restriction, being distributed along the complete elevation gradient. The open low woodland with shrubs was the only restricted physiognomy, significantly absent from the upper part of the gradient. Conclusions We highlight the importance of considering the two vegetation properties independently when characterizing vegetation patterns in heterogeneous systems, since they show decoupled responses to environmental gradients. We note that the assumption of a direct link between floristic composition and physiognomy may induce bias into the understanding of vegetation patterns and processes. Hence, we encourage managers and restoration practitioners to consider the complete range of possible physiognomic types under each floristic type. [ABSTRACT FROM AUTHOR]

The present work investigates the fluid dynamic distribution in two different geometries of Microbial Fuel Cells (MFCs), a squared shape MFC and a drop-like one, and explores their use as possible biosensors. For both architectures, air-cathode single chamber microbial fuel cells (SCMFCs) with an inner volume of 12.5 mL have been developed. Simulations based on Navier-Stokes equations were used to investigate the motion of fluid, i.e., the electrolyte, inside the MFCs. The aim was to define the effective exposed area for each introduced architecture, and to correlate this parameter to the variation of the device performances in terms of current densities, together with their response to the variation of sodium acetate concentration. For this purpose, the fluid dynamic simulations have been implemented using two different flow rate values, namely, 12.5 mL h−1 and 100 mL h−1. The experimental amperometric response of drop-like SCMFCs and squared shape SCMFCs, fabricated by 3D printing, have been correlated with the variation of sodium acetate concentration and the relative sensitivity analyzed. The optimized drop-like SCMFC showed the better behavior, with an effective concentration of sodium acetate close to the nominal one and an improved sensitivity for high flow rates. [ABSTRACT FROM AUTHOR]

Livestock grazing represents an important human disturbance for vegetation worldwide. We analysed the intraspecific differences in mean trait values between different grazing regimes (ungrazed and grazed) and explored whether these differences are consistent across species in a sub-humid mountain ecosystem in Central Argentina. We selected 14 species of eight different families, co-occurring in both regimes and comprising herbaceous (grasses and forbs) and woody (shrubs and trees) plants. For each species and grazing regime we measured 12 traits related to plant size, carbon fixation and water use. We found that plants in the grazed regime had consistently smaller leaves and shorter stature and internodal length than plants of the same species under the ungrazed regime. For the remaining traits the responses were species-specific. Dry matter content, leaf tensile strength and minimum leaf water potential (Ψleaf) showed contrasting responses to grazing. Specific leaf area, wood density and potential water content of wood showed almost no significant responses except for very few species. Neither leaf area per shoot mass nor leaf area per sapwood area differed significantly between grazing regimes. Our study suggested that the intraspecific variation found for the size-related traits would allow species to respond to grazing without modifying markedly other structural traits, a plastic response that might increase the probability of species success. [ABSTRACT FROM AUTHOR]

The article looks at a study which demonstrate cellulose fiber networks can be sized or compounded with cellulose acetate (CA) graphene based composites for avoiding the use of any plasticizers for abrasion resistant biocomposite electrical conductors. It mentions use of graphene nanoplatelet (GnPs) and flexible nanocomposites with electric conductivity. It also mentions use of surface electromyography and electromagnetic interference (EMI) shields for high speed electronics.

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Myocardial stretch elicits a biphasic contractile response: the Frank–Starling mechanism followed by the slow force response (SFR) or Anrep effect. In this study we hypothesized that the SFR depends on epidermal growth factor receptor (EGFR) transactivation after the myocardial stretch-induced angiotensin II (Ang II)/endothelin (ET) release. Experiments were performed in isolated cat papillary muscles stretched from 92 to 98% of the length at which maximal twitch force was developed ( Lmax). The SFR was 123 ± 1% of the immediate rapid phase ( n= 6, P < 0.05) and was blunted by preventing EGFR transactivation with the Src-kinase inhibitor PP1 (99 ± 2%, n= 4), matrix metalloproteinase inhibitor MMPI (108 ± 4%, n= 11), the EGFR blocker AG1478 (98 ± 2%, n= 6) or the mitochondrial transition pore blocker clyclosporine (99 ± 3%, n= 6). Stretch increased ERK1/2 phosphorylation by 196 ± 17% of control ( n= 7, P < 0.05), an effect that was prevented by PP1 (124 ± 22%, n= 7) and AG1478 (131 ± 17%, n= 4). In myocardial slices, Ang II (which enhances ET mRNA) or endothelin-1 (ET-1)-induced increase in O2− production (146 ± 14%, n= 9, and 191 ± 17%, n= 13, of control, respectively, P < 0.05) was cancelled by AG1478 (94 ± 5%, n= 12, and 98 ± 15%, n= 8, respectively) or PP1 (100 ± 4%, n= 6, and 99 ± 8%, n= 3, respectively). EGF increased O2− production by 149 ± 4% of control ( n= 9, P < 0.05), an effect cancelled by inhibiting NADPH oxidase with apocynin (110 ± 6% n= 7), mKATP channels with 5-hydroxydecanoic acid (5-HD; 105 ± 5%, n= 8), the respiratory chain with rotenone (110 ± 7%, n= 7) or the mitochondrial permeability transition pore with cyclosporine (111 ± 10%, n= 6). EGF increased ERK1/2 phosphorylation (136 ± 8% of control, n= 9, P < 0.05), which was blunted by 5-HD (97 ± 5%, n= 4), suggesting that ERK1/2 activation is downstream of mitochondrial oxidative stress. Finally, stretch increased Ser703 Na+/H+ exchanger-1 (NHE-1) phosphorylation by 172 ± 24% of control ( n= 4, P < 0.05), an effect that was cancelled by AG1478 (94 ± 17%, n= 4). In conclusion, our data show for the first time that EGFR transactivation is crucial in the chain of events leading to the Anrep effect. [ABSTRACT FROM AUTHOR]

When the length of the myocardium is increased, a biphasic response to stretch occurs involving an initial rapid increase in force followed by a delayed slow increase called the slow force response (SFR). Confirming previous findings involving angiotensin II in the SFR, it was blunted by AT1 receptor blockade (losartan). The SFR was accompanied by an increase in reactive oxygen species (ROS) of ∼30% and in intracellular Na+ concentration ([Na+]i) of ∼2.5 mmol l−1 over basal detected by H2DCFDA and SBFI fluorescence, respectively. Abolition of ROS by 2-mercapto-propionyl-glycine (MPG) and EUK8 suppressed the increase in [Na+]i and the SFR, which were also blunted by Na+/H+ exchanger (NHE-1) inhibition (HOE642). NADPH oxidase inhibition (apocynin or DPI) or blockade of the ATP-sensitive mitochondrial potassium channels (5HD or glybenclamide) suppressed both the SFR and the increase in [Na+]i after stretch, suggesting that endogenous angiotensin II activated NADPH oxidase leading to ROS release by the ATP-sensitive mitochondrial potassium channels, which promoted NHE-1 activation. Supporting the notion of ROS-mediated NHE-1 activation, stretch increased the ERK1/2 and p90rsk kinases phosphorylation, effect that was cancelled by losartan. In agreement, the SFR was cancelled by inhibiting the ERK1/2 signalling pathway with PD98059. Angiotensin II at a dose that mimics the SFR (1 nmol l−1) induced an increase in ·O2− production of ∼30–40% detected by lucigenin in cardiac slices, an effect that was blunted by losartan, MPG, apocynin, 5HD and glybenclamide. Taken together the data suggest a pivotal role of mitochondrial ROS in the genesis of the SFR to stretch. [ABSTRACT FROM AUTHOR]

Objectives The aims of this study were to identify temporal trends in the incidence of sexually transmitted diseases ( STDs) in a cohort of HIV-infected people and to evaluate factors associated with the risk of a new STD diagnosis. Methods All HIV-infected patients in the Icona Foundation Study cohort enrolled after 1998 were included in this study. STD incidence rates ( IRs) were calculated and stratified by calendar period. Predictors of STDs were identified using a Poisson regression model with sandwich estimates for standard errors. Results Data for 9168 participants were analysed [median age 37.3 (range 18-81) years; 74% male; 30% men who have sex with men ( MSM)]. Over 46 736 person-years of follow-up ( PYFU), 996 episodes of STDs were observed [crude IR 21.3/1000 PYFU; 95% confidence interval ( CI) 20.0-22.6/1000 PYFU]. In multivariable Poisson regression analysis, MSM [rate ratio ( RR) 3.03; 95% CI 2.52-3.64 versus heterosexuals], calendar period ( RR 1.67; 95% CI 1.42-1.97 for 2008-2012 versus 1998-2002), HIV RNA > 50 HIV-1 RNA copies/mL ( RR 1.44; 95% CI 1.19-1.74 versus HIV RNA ≤ 50 copies/mL) and a current CD4 count < 100 cells/μL ( RR 4.66; 95% CI 3.69-5.89; P < 0.001 versus CD4 count > 500 cells/μL) were associated with an increased risk of STDs. In contrast, older age ( RR 0.82 per 10 years older; 95% CI 0.77-0.89) and being currently on ART ( RR 0.38; 95% CI 0.33-0.45) compared with being ART-naïve or on a treatment interruption were associated with a lower risk of developing STDs. Conclusions An increase in the incidence of STDs was observed in more recent years. Interventions to prevent STDs and potential spread of HIV should target the younger population, MSM and people currently not receiving ART. [ABSTRACT FROM AUTHOR]

Aim The relationship between airway hyper-responsiveness ( AHR) and atopy has been previously investigated, but there are still some issues to be clarified. The aim of this study was to assess the link between AHR and mannitol and atopy in asthmatic children. Methods We evaluated 44 children with asthma, aged 6-16 years of age, using skin prick tests ( SPTs), serum total and specific immunoglobulin E (IgE) levels and the mannitol challenge test ( MCT). Results We found a good correlation between AHR to mannitol and specific IgE against Dermatophagoides pteronissinus (r = −0.66, p < 0.001) and a weak correlation with specific IgE against dog dander (r = −0.33, p = 0.01) and Aspergillus fumigatus (r = −0.23, p = 0.02). Furthermore, we found a weak correlation between AHR to mannitol and serum total IgE (r = −0.30; p = 0.03), the sum of specific IgE to aeroallergens (r = −0.37, p = 0.01) and the number of positive SPTs (r = −0.31, p = 0.02). Conclusion Measuring AHR with MCT might provide an accurate evaluation of the degree of atopy in children. The patients with a higher degree of atopy were significantly more reactive to mannitol. In clinical practice, these results indicate that children with asthma who are more atopic may require more intensive treatment strategies to reduce AHR. [ABSTRACT FROM AUTHOR]

In this study we assessed the water transport strategies and the abundance of alien and native tree species at a regional scale in Córdoba Mountains, Central Argentina. The aims of this study were: (i) to analyse whether alien and native tree species show divergent water transport strategies; and (ii) to explore whether species abundances of alien and natives are associated with specific trait attributes. Eight alien species and 12 native species were recorded in 50 complete vascular plant vegetation relevés. Water transport strategies were assessed through the following functional traits: minimum leaf water potential, potential water content of wood, effective leaf area, leaf area per sapwood area and wood density. Also, resource use strategies were assessed throughout the measurement of specific leaf area. We found that alien species had a higher efficiency in water transport (i.e. higher minimum leaf water potential and lower wood density values) and faster resource acquisition and use (higher specific leaf area values) than native species. We did not find evidence suggesting that the relative abundance of species was associated to water transport strategies and faster resource acquisition and use. Alien species seem to differ from natives in specific functional attributes that are absent in the resident community and might allow aliens to use more resources and at a higher rate than native species. Finally, our results show the potential of a trait-based predictive framework for alien species, and the possible effects on ecosystem functions. [ABSTRACT FROM AUTHOR]

Early electrical activity and calcium influx regulate crucial aspects of neuronal development. Small-conductance calcium-activated potassium (SK) channels regulate action potential firing and shape calcium influx through feedback regulation in mature neurons. These functions, observed in the adult nervous system, make them ideal candidates to regulate activity- and calcium-dependent processes in neurodevelopment. However, to date little is known about the onset of expression and regions expressing SK channel subunits in the embryonic and postnatal development of the central nervous system (CNS). To allow studies on the contribution of SK channels to different phases of development of single neurons and networks, we have performed a detailed in situ hybridization mapping study, providing comprehensive distribution profiles of all three SK subunits (SK1, SK2, and SK3) in the rat CNS during embryonic and postnatal development. SK channel transcripts are expressed at early stages of prenatal CNS development. The three SK channel subunits display different developmental expression gradients in distinct CNS regions, with time points of expression and up- or downregulation that can be associated with a range of diverse developmental events. Their early expression in embryonic development suggests an involvement of SK channels in the regulation of developmental processes. Additionally, this study shows how the postnatal ontogenetic patterns lead to the adult expression map for each SK channel subunit and how their coexpression in the same regions or neurons varies throughout development. J. Comp. Neurol. 522:1072-1101, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]