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The benefits of sustainability reporting are indisputable. These include, first and foremost, building trust. Transparency on non-financial performance can help reduce reputational risk and open a dialogue with stakeholders. Transparent sustainability reporting is also a sign of openness and responsibility. Efforts to develop the economy sustainably include the development of reporting concepts in this sphere. Sustainability activities are becoming an increasingly important element of business reports. This article aims to present and verify the current sustainability reporting at the level of comparison of reported indicators of selected automotive companies in the context of the most widely used Global Reporting Initiative systematics and the upcoming requirements defined by the Corporate Sustainability Reporting Directive (CSRD). It focuses on study cases and identifies good practices and difficulties of sustainable reporting in the automotive industry. This study used the case study method on selected automotive industry companies. The case study analyses a defined problem consisting of a real situation and information as a methodological tool. The findings show that the world’s major automotive companies are broadly endeavouring to realise sustainability practices. The main conclusion of the analysis is that the Environmental, Social, and Governance (ESG) framework and the Global Reporting Initiative (GRI), in addition to being complementary, can be combined not only to improve the strategic management of an organisation but also, in a broader context, serve the well-being of the local community and society at large. The article organises and systematises knowledge about the ESG concept and the GRI standard, which currently play an important role in sustainability reporting.

We demonstrate a novel method for the stable and selective surface functionalization of germanium (Ge) embedded in silicon dioxide. The Ge(001) surface is functionalized using α-lipoic acid (ALA), which can potentially be utilized for the immobilization of a wide range of biomolecules. We present a detailed pH-dependence study to establish the effect of the incubation pH value on the adsorption layer of the ALA molecules. A threshold pH value for functionalization is identified, dividing the examined pH range into two regions. Below a pH value of 7, the formation of a disordered ALA multilayer is observed, whereas a stable well-ordered ALA mono- to bi-layer on Ge(001) is achieved at higher pH values. Furthermore, we analyze the stability of the ALA layer under ambient conditions, revealing the most stable functionalized Ge(001) surface to effectively resist oxidation for up to one week. Our established functionalization method paves the way towards the successful immobilization of biomolecules in future Ge-based biosensors. [ABSTRACT FROM AUTHOR]

In the present work the analysis of the magnetization reversal processes based on the measurements of recoil curves were studied. Two series of specimens of Nd-Fe-B-type alloy were investigated: (i) meltspun ribbons and (ii) mechanically alloyed magnets. It was shown that in both cases annealing of the samples causes change of the magnetic properties. This is an effect of the evolution of the microstructure and phase constitution driven by the annealing. Based on the recoil curves measurements the Mrev (Mirr) curves were constructed. Furthermore, the minor hysteresis loops allowed to determine the dependences of coercivity on the maximum external magnetic field. These two approaches allowed concluding about the magnetization reversal processes. [ABSTRACT FROM AUTHOR]

In most organisms, cells typically maintain genome integrity, as radical genome reorganization leads to dramatic consequences. However, certain organisms, ranging from unicellular ciliates to vertebrates, are able to selectively eliminate specific parts of their genome during certain stages of development. Moreover, partial or complete elimination of one of the parental genomes occurs in interspecies hybrids reproducing asexually. Although several examples of this phenomenon are known, the molecular and cellular processes involved in selective elimination of genetic material remain largely undescribed for the majority of such organisms. Here, we elucidate the process of selective genome elimination in water frog hybrids from the Pelophylax esculentus complex reproducing through hybridogenesis. Specifically, in the gonads of diploid and triploid hybrids, but not those of the parental species, we revealed micronuclei in the cytoplasm of germ cells. In each micronucleus, only one centromere was detected with antibodies against kinetochore proteins, suggesting that each micronucleus comprises a single chromosome. Using 3D-FISH with species-specific centromeric probe, we determined the role of micronuclei in selective genome elimination. We found that in triploid LLR hybrids, micronuclei preferentially contain P. ridibundus chromosomes, while in diploid hybrids, micronuclei preferentially contain P. lessonae chromosomes. The number of centromere signals in the nuclei suggested that germ cells were aneuploid until they eliminate the whole chromosomal set of one of the parental species. Furthermore, in diploid hybrids, misaligned P. lessonae chromosomes were observed during the metaphase stage of germ cells division, suggesting their possible elimination due to the inability to attach to the spindle and segregate properly. Additionally, we described gonocytes with an increased number of P. ridibundus centromeres, indicating duplication of the genetic material. We conclude that selective genome elimination from germ cells of diploid and triploid hybrids occurs via the gradual elimination of individual chromosomes of one of the parental genomes, which are enclosed within micronuclei. [ABSTRACT FROM AUTHOR]

Marta Masternak,1 Bartosz Puła,2 Joanna Knap,1 Anna Waszczuk-Gajda,3 Joanna Drozd-Sokołowska,3 Kamil Wdowiak,4 Sebastian Grosicki,5 Izabela Kozłowska,6 Marta Kaźmierczak,6 Anna Łabędź,7 Łukasz Szukalski,8 Kamil Wiśniewski,2 Edyta Subocz,9 Janusz Hałka,10 Agnieszka Szymczyk,11 Marek Hus,12 Krzysztof Jamroziak,2 Krzysztof Giannopoulos13 1Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland; 2Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland; 3Department of Hematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland; 4Department of Internal Medicine and Oncological Chemotherapy, Silesian Medical University, Katowice, Poland; 5Department of Hematology and Cancer Prevention in Chorzow, Faculty of Health Sciences in Bytom, Silesian Medical University, Katowice, Poland; 6Department of Hematology and Cancer Prevention, Municipal Hospital in Chorzów, Chorzów, Poland; 7Department of Hematology, Rydrygier’s Hospital in Cracow, Cracow, Poland; 8Department of Hematology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Toruń, Poland; 9Department of Hematology, Military Institute of Medicine, Warsaw, Poland; Clinical Department of Hematology, Independent Public Healthcare Centre of the Ministry of Internal Affairs and Administration with Warmia-Mazury Region’s Oncology Centre in Olsztyn, Olsztyn, Poland; 10Clinical Department of Hematology, Independent Public Healthcare Centre of the Ministry of Internal Affairs and Administration with Warmia-Mazury Region’s Oncology Centre in Olsztyn, Olsztyn, Poland; 11Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland; Hematology Department, St John’s Cancer Center, Lublin, Poland; 12Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland; 13Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland; Hematology Department, St John’s Cancer Center, Lublin, PolandCorrespondence: Krzysztof Giannopoulos Tel +48 81448 6632Fax +48 81448 6634Email krzysztof.giannopoulos@gmail.comPurpose: Mean platelet volume (MPV) is a readily accessible and commonly tested hematological indicator. Recent studies revealed a significant impact of MPV on the course and prognosis of many diseases, including some types of cancer, as well as on the incidence of atrial fibrillation and bleeding. The study aimed to perform a retrospective analysis of MPV in terms of time to first treatment (TTFT) and to determine its prognostic value in the group of patients with chronic lymphocytic leukemia (CLL). Moreover, the study includes a retrospective analysis of platelet parameters in patients treated with ibrutinib concerning bleeding and atrial fibrillation.Patients and Methods: The study included 523 patients with CLL, for 344 the most important cytogenetic aberrations were reported. The Mann–Whitney, Kruskal–Wallis, Kaplan–Meier, chi-squared, log‑rank tests and multivariate Cox proportional hazard regression model were used to analyze collected data.Results: The receiver operating characteristic curve analysis was performed to identify optimal cut-off value for MPV. The analysis of survival curves showed that in the group of patients with higher values of MPV TTFT was significantly longer than in the group with lower MPV (17.9 vs 36 months, p=0.0015, cut-off value for MPV= 10.4 fl). In multivariate Cox proportional hazard regression model low MPV, the presence of del11q and del13q provided independent prognostic value for TTFT (HR=0.69, 95%-CI, 0.5293 to 0.9081; p=0.0078; HR=1.76, 95%-CI, 1.3000 to 2.3882, p=0.0003, HR=0.74, 95%-Cl, 0.5674 to 0.9588, p=0.0229, respectively). In the group treated with ibrutinib, 59 patients had no significant correlation between MPV level and the incidence of therapy complications, although in the group of patients with low MPV there was a tendency for more frequent occurrence of atrial fibrillation (p=0.259).Conclusion: Low MPV values are associated with unfavorable prognosis and might represent a novel, independent prognostic factor in CLL.Keywords: MPV, chronic lymphocytic leukemia, TTFT

In the following article the magnetic properties and phase composition of (Nd10Fe67B23)100-xNbx (where x = 5, 6, 7, 8, 9) alloys in the form of ribbons are discussed. The X-ray diffraction studies revealed the coexistence of amorphous and nanocrystalline structures consisting of Nd2Fe14B, Nd1+"Fe4B4 and metastable Nd2Fe23B3 phases. The shape of Mrev (Mirr) suggests that the magnetization reversal proceeds through the nucleation of the reversal domain for the ribbon doped with 5-7 at.% of Nb and the subsequent pinning of the domain walls for ribbons doped with 8 and 9 at.% of Nb. [ABSTRACT FROM AUTHOR]

Parasitic infections are widespread among exotic lizards and cause serious problems in both private captive breeding and trade networks. Among 168 lizards obtained from captive breeding (Zoological Garden in Wrocław and private owners) and trade (pet shops and wholesale) the total prevalence of endoparasites was 42.35 %. We detected species of Protozoa, Cestoda, Trematoda - Digenea and Nematoda as well as pseudoparasites. The prevalence of endoparasites was higher in the reptiles obtained from captive breeding (59.5 %) than in those from trade network, however the parasite species spectrum was wider in the animals form pet shops and wholesales.

Non-intensive therapies such as the hypomethylating agent (HMA) azacitidine (AZA) have been used in patients with AML ineligible for intensive induction chemotherapy (IC) or stem cell transplant due to advanced age, comorbidities, and/or risk factors. However, response rates and survival remain dismal. Pre-clinical studies indicate the epigenetic combination of HMAs and HDAC inhibitors induce re-expression of silenced genes synergistically. The activity of pracinostat, an oral pan-HDAC inhibitor, has been shown in xenograft tumor models of AML and promising efficacy was seen in a Phase 2 study. This Phase 3 study (NCT03151408) evaluated the efficacy/safety of pracinostat administered with AZA in adult patients with newly diagnosed AML ineligible to receive IC. Patients were randomized to either pracinostat plus AZA or placebo/AZA and stratified by cytogenetic risk and ECOG status. As planned, an interim analysis was performed when 232/390 events (deaths) occurred. A total of 406 patients were randomized (203/group) at the time of the analysis. Median overall survival was 9.95 months for both treatment groups (p=0.8275). There was no significant difference between treatments in secondary efficacy endpoints, reflecting a lack of clinical response. This study did not show a benefit of adding pracinostat to AZA in elderly patients unfit for IC., Competing Interests: Declaration of Competing Interest GGM has nothing to disclose. MK has received honoraria from Sanofi and Takeda. AW has received research grants from Jazz Pharmaceuticals; honoraria from AbbVie, Astellas, BMS/Celgene, Gilead/Kite, Janssen, Novartis, Pfizer, and Servier; and has participated in advisory boards for AbbVie, Astellas, BerGenBio, BMS/Celgene, Gilead/Kite, Janssen, Novartis, Pfizer, and Servier. CYF has received honoraria from Abbvie, Amgen, Beigene, Bristol-Myers Squibb, Jazz, Novartis, Pfizer and Servier; has acted as a consultant/advisor for Abbvie, Amgen, Astellas Pharma, Bristol-Myers Squibb, Jazz, Novartis, Pfizer and Servier; and has received research funding from Amgen, Astellas and Jazz. MKK has nothing to disclose. GB was an employee of Helsinn Healthcare during the conduct of the study and development of the manuscript. FS was an employee of Helsinn Healthcare during the conduct of the study and development of the manuscript. LA has acted as a consultant/advisor for Helsinn Healthcare, BMS, Novartis, JAZZ, Amgen, Roche, Curis, Kura and Abbvie and has received research funding from BMS and Abbvie., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In the face of flourishing industrialization and global trade, heavy metal and metalloid contamination of the environment is a growing concern throughout the world. The widespread presence of highly toxic compounds of arsenic, antimony, and cadmium in nature poses a particular threat to human health. Prolonged exposure to these toxins has been associated with severe human diseases, including cancer, diabetes, and neurodegenerative disorders. These toxins are known to induce analogous cellular stresses, such as DNA damage, disturbance of redox homeostasis, and proteotoxicity. To overcome these threats and improve or devise treatment methods, it is crucial to understand the mechanisms of cellular detoxification in metal and metalloid stress. Membrane proteins are key cellular components involved in the uptake, vacuolar/lysosomal sequestration, and efflux of these compounds; thus, deciphering the multilevel regulation of these proteins is of the utmost importance. In this review, we summarize data on the mechanisms of arsenic, antimony, and cadmium detoxification in the context of membrane proteome. We used yeast Saccharomyces cerevisiae as a eukaryotic model to elucidate the complex mechanisms of the production, regulation, and degradation of selected membrane transporters under metal(loid)-induced stress conditions. Additionally, we present data on orthologues membrane proteins involved in metal(loid)-associated diseases in humans.

With the COVID-19 pandemic, behavioural scientists aimed to illuminate reasons why people comply with (or not) large-scale cooperative activities. Here we investigated the motives that underlie support for COVID-19 preventive behaviours in a sample of 12,758 individuals from 34 countries. We hypothesized that the associations of empathic prosocial concern and fear of disease with support towards preventive COVID-19 behaviours would be moderated by trust in the government. Results suggest that the association between fear of disease and support for COVID-19 preventive behaviours was strongest when trust in the government was weak (both at individual- and country-level). Conversely, the association with empathic prosocial concern was strongest when trust in the government was high, but this moderation was only found at individual-level scores of governmental trust. We discuss how motivations may be shaped by socio-cultural context, and outline how findings may contribute to a better understanding of collective action during global crises., (© 2023. The Author(s).)

Background: Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) was passed by the European Parliament and the Council of the European Union on 5 April 2017 and came into force on 26 May 2017. A new amending regulation, which introduces a phased implementation of the IVDR with new transitional provisions for certain in vitro diagnostic medical devices (IVDs) and a later date of application of some requirements for in-house devices for healthcare facilities, was adopted on 15 December 2021. The combined use of CE-certified IVDs (CE-IVDs), in-house IVDs (IH-IVDs), and research use only (RUO) devices are a cornerstone of diagnostics in pathology departments and crucial for optimal patient care. The IVDR not only regulates the manufacture and placement on the market of industrially manufactured IVDs, but also imposes conditions on the manufacture and use of IH-IVDs for internal use by healthcare facilities., Objectives: Our work provides an overview of the background and structure of the IVDR and identifies core areas that need to be interpreted and fleshed out in the context of the legal framework as well as expert knowledge., Conclusions: The gaps and ambiguities in the IVDR crucially require the expertise of professional societies, alliances, and individual stakeholders to successfully facilitate the implementation and use of the IVDR in pathology departments and to avoid aberrant developments., (© 2023. The Author(s).)

Purpose: Zanubrutinib is a potent, irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target kinase inhibition. We hypothesized that complete/sustained BTK occupancy may improve efficacy outcomes and increased BTK specificity may minimize off-target inhibition-related toxicities., Patients and Methods: ALPINE (ClinicalTrials.gov identifier: NCT03734016) is a global, randomized, open-label phase III study of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia. The primary end point was investigator-assessed overall response rate (ORR). The preplanned interim analysis was scheduled approximately 12 months after the first 415 patients were enrolled., Results: Between November 1, 2018, and December 14, 2020, 652 patients were enrolled. We present the interim analysis of the first 415 enrolled patients randomly assigned to receive zanubrutinib (n = 207) or ibrutinib (n = 208). At 15 months of median follow-up, ORR (partial or complete response) was significantly higher with zanubrutinib (78.3%; 95% CI, 72.0 to 83.7) versus ibrutinib (62.5%; 95% CI, 55.5 to 69.1; two-sided P < .001). ORR was higher with zanubrutinib versus ibrutinib in subgroups with del(17p)/ TP53 mutations (80.5% v 50.0%) and del(11q) (83.6% v 69.1%); 12-month progression-free survival in all patients was higher with zanubrutinib (94.9%) versus ibrutinib (84.0%; hazard ratio, 0.40; 95% CI, 0.23 to 0.69). Atrial fibrillation rate was significantly lower with zanubrutinib versus ibrutinib (2.5% v 10.1%; two-sided P = .001). Rates of cardiac events, major hemorrhages, and adverse events leading to treatment discontinuation/death were lower with zanubrutinib., Conclusion: Zanubrutinib had a significantly higher ORR, lower atrial fibrillation rate, and improved progression-free survival and overall cardiac safety profile versus ibrutinib. These data support improved efficacy/safety outcomes with selective BTK inhibition.

Background: Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) was passed by the European Parliament and the Council of the European Union on 5 April 2017 and came into force on 26 May 2017. A new amending regulation, which introduces a phased implementation of the IVDR with new transitional provisions for certain in vitro diagnostic medical devices and a later date of application of some requirements for in-house devices for healthcare facilities, was adopted on 15 December 2021. The combined use of CE-IVDs, in-house IVDs, and RUO products are a cornerstone of diagnostics in pathology departments and crucial for optimal patient care. The IVDR not only regulates the manufacture and placement on the market of industrially manufactured IVDs, but also imposes conditions on the manufacture and use of IH-IVDs for internal use by healthcare facilities., Objectives: Our work provides an overview of the background and structure of the IVDR and identifies core areas that need to be interpreted and fleshed out in the context of the legal framework as well as expert knowledge., Conclusions: The gaps and ambiguities in the IVDR crucially require the expertise of professional societies, alliances, and individual stakeholders to successfully facilitate the implementation and use of the IVDR in pathology departments and to avoid aberrant developments., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Vital signs (VS) are used to triage and identify children at risk for severe illness. Few studies have examined the association of pediatric VS at emergency department (ED) discharge with patient outcomes., Objective: To determine if children discharged from the ED with abnormal VS have high rates of return visits, admission or adverse outcomes., Methods: We conducted a retrospective cohort study of children discharged from 2 pediatric EDs with abnormal VS between July 2018-June 2019. We queried electronic health records (EHR) for children ages 0-18 years discharged from the ED with abnormal last recorded VS. VS were considered erroneously entered and thus excluded from analysis if heart rate was <30 or ≥ 300, respiratory rate was 0 or ≥ 100 or oxygen saturation was <50. Patients who were declared deceased at index visit were excluded. Demographic, clinical, and outcome data including return visits within 48 h and adverse outcomes after the initial ED discharge were obtained., Results: Of the 97,824 children evaluated in the EDs during the study period, 17,661 (18.1%) were discharged with abnormal VS. 404 (2.28%) returned to the ED, of which 95 (23.5%) were admitted for the same chief complaint within 48 h. In comparison, the 48-h return rate for children discharged with normal VS was 2.45% (p = 0.219). Children discharged with abnormal VS were more likely to return if they had 2 or more abnormal VS (OR 1.6; 95% CI 1.23-2.07), were less than 3 years old (OR 1.69, 95% CI 1.39-2.06) or their initial acuity level was high (OR 1.34; 95% CI 1.1-1.63). Higher initial acuity level and age less than 3 years were also associated with admission at revisit (OR 2.58; 95% CI 1.59-4.2; OR 2.20, 95% CI 1.36-3.55). Four of the children who returned required PICU admission, but none died, required CPR or endotracheal intubation., Conclusion: Although many children were discharged from the ED with abnormal VS, few returned and required admission. Having 2 or more abnormal VS, age less than 3 years and higher acuity increased odds of revisit. Few children suffered serious adverse outcomes., Competing Interests: Declaration of Competing Interest The authors have no disclosures or conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This systematic review and meta-analysis aimed to determine mean estimates of prevalence rates for fulfilling all diagnostic criteria of posttraumatic stress disorder (PTSD) or at least showing significant levels of posttraumatic stress (PTSS) in relation to the traumatic event of childbirth. For the first time, both mothers and fathers were included in the synthesis. Studies were identified through systematic database search and manual searches, irrespective of language. Meta-analyses of 154 studies (N = 54,711) applied a random-effects model to four data sets, resulting in pooled prevalence rates of 4.7% for PTSD and 12.3% for PTSS in mothers. Lower rates of 1.2% for PTSD and 1.3% for PTSS were found among fathers. Subgroup analyses showed elevated rates in targeted samples (those with a potential risk status) most distinctly for maternal PTSS. The significant amount of heterogeneity between studies could not be explained to a satisfactory degree through meta-regression. Given the substantial percentage of affected parents, the adoption of adequate prevention and intervention strategies is needed. As this field of research is evolving, attention should be broadened to the whole family system, which may directly and indirectly be affected by birth-related PTSD. Further studies on paternal PTSD/PTSS are particularly warranted., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Maternal prenatal anxiety is among important public health issues as it may affect child development. However, there are not enough studies to examine the impact of a mother's anxiety on the child's early development, especially up to 1 year. Objective: The present prospective cohort study aimed to examine whether maternal trait anxiety, perceived social support, and COVID-19 related fear impacted speech-language, sensory-motor, and socio-emotional development in 12 months old Serbian infants during the COVID-19 pandemic. Methods: This follow-up study included 142 pregnant women (Time 1) and their children at 12 months (Time 2). Antenatal maternal anxiety and children's development were examined. Maternal anxiety was assessed using the State-Trait Anxiety Inventory (STAI). Child speech-language, sensory-motor, and socio-emotional development were assessed using the developmental scale in the form of an online questionnaire that examined the early psychophysiological child development. Information on socioeconomic factors, child and maternal demographics, clinical factors, and perceived fear of COVID-19 viral infection were collected. Multivariable General Linear Model analysis was conducted, adjusted for demographic, clinical, and coronavirus prenatal experiences, maternal prenatal anxiety levels, perceived social support, speech-language, motor skills, and cognitive and socio-emotional development at the infants' age of 12 months. Results: The study revealed the influence of the COVID-19 pandemic on maternal trait anxiety. The association between selected independent factors and infants' development was found in a demographically unified sample except for employment and the number of children. There was a correlation between all observed developmental functions. Univariate General Linear model statistical analysis indicated that linear models with selected independent factors and covariates could account for 30.9% (Cognition) up to 40.6% (Speech-language) of variability in developmental functions. It turned out that two-way and three-way interactions had a dominant role on models, and STAI-T Level and COVID-19 related fear were present in all interaction terms. Conclusion: Our findings reveal important determinants of child developmental outcomes and underline the impact of maternal anxiety on early child development. These findings lay the groundwork for the following interdisciplinary research on pregnancy and child development to facilitate and achieve positive developmental outcomes and maternal mental health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer ML declared a shared affiliation, with no collaboration, with one of the authors MK to the handling editor at the time of the review., (Copyright © 2021 Jeličić, Sovilj, Bogavac, Drobnjak, Gouni, Kazmierczak and Subotić.)

Despite the fact that there is a growing awareness to the callosal connections between hemispheres the two hemispheres of the brain are commonly treated as independent structures when peripheral or cortical manipulations are applied to one of them. The contralateral hemisphere is often used as a within-animal control of plastic changes induced onto the other side of the brain. This ensures uniform conditions for producing experimental and control data, but it may overlook possible interhemispheric interactions. In this paper we provide, for the first time, direct proof that cortical, experience-dependent plasticity is not a unilateral, independent process. We mapped metabolic brain activity in rats with 2-[ 14 C] deoxyglucose (2DG) following experience-dependent plasticity induction after a month of unilateral (left), partial whiskers deprivation (only row B was left). This resulted in ∼45% widening of the cortical sensory representation of the spared whiskers in the right, contralateral barrel field (BF). We show that the width of 2DG visualized representation is less than 20% when only contralateral stimulation of the spared row of whiskers is applied in immobilized animals. This means that cortical map remodeling, which is induced by experience-dependent plasticity mechanisms, depends partially on the contralateral hemisphere. The response, which is observed by 2DG brain mapping in the partially deprived BF after standard synchronous bilateral whiskers stimulation, is therefore the outcome of at least two separately activated plasticity mechanisms. A focus on the integrated nature of cortical plasticity, which is the outcome of the emergent interactions between deprived and non-deprived areas in both hemispheres may have important implications for learning and rehabilitation. There is also a clear implication that there is nothing like "control hemisphere" since any plastic changes in one hemisphere have to have influence on functioning of the opposite one., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jablonka, Binkowski, Kazmierczak, Sadowska, Sredniawa, Szlachcic and Urban.)

Objectives : In the three experimental conditions we examined the role of the exposure to recorded infant's cry (at high and at lower frequency) or laughter and the level of participants' general self-efficacy on emotional reactions to the infant's cry. Background : Infant's cry can trigger empathic, sensitive responses or elicit frustration and anxiety of the caregiver. General caregiver's self-efficacy serves as a predictor of more sensitive reactions to distress cues of a child. Method : An experimental study with three conditions - exposure to infant cry at high frequency, infant cry at lower frequency or infant laughter, was conducted on the sample of 192 childless undergraduates. Exposure to the selected stimulus was preceded by the General Self-Efficacy Scale and followed by the My Emotions Scale for the assessment of participants' emotional reactions to the presented infant crying or laughter. Results : Participants with high self-efficacy exposed to the child's cry at high frequency presented the highest level of child-oriented emotional reactions and lower level of self-oriented reactions as compared to participants with low self-efficacy. Conclusion : Results suggest that general self-efficacy can serve as a supportive factor in sensitive responding to the high-frequency cry. Improving caregivers' self-efficacy can reduce the risk of insensitive, disturbed parenthood.

The expression of apoptosis-related BCL2 family genes, fine-tuned in normal cells, is dysregulated in many neoplasms. In acute myeloid leukemia (AML), this problem has not been studied comprehensively. To address this issue, RNA-seq data were used to analyze the expression of 26 BCL2 family members in 27 AML FAB M1 and M2 patients, divided into subgroups differently responding to chemotherapy. A correlation analysis, analysis of variance, and Kaplan-Meier analysis were applied to associate the expression of particular genes with other gene expression, clinical features, and the presence of mutations detected by exome sequencing. The expression of BCL2 family genes was dysregulated in AML, as compared to healthy controls. An upregulation of anti-apoptotic and downregulation of pro-apoptotic genes was observed, though only a decrease in BMF , BNIP1 , and HRK was statistically significant. In a group of patients resistant to chemotherapy, overexpression of BCL2L1 was manifested. In agreement with the literature data, our results reveal that BCL2L1 is one of the key players in apoptosis regulation in different types of tumors. An exome sequencing data analysis indicates that BCL2 family genes are not mutated in AML, but their expression is correlated with the mutational status of other genes, including those recurrently mutated in AML and splicing-related. High levels of some BCL2 family members, in particular BIK and BCL2L13 , were associated with poor outcome.

Metabolomics, the systematic investigation of metabolites in biological fluids, cells, or tissues, reveals essential information about metabolism and diseases. Metabolites have functional roles in a myriad of biological processes, as substrates and products of enzymatic reactions but also as cofactors and regulators of large numbers of biochemical mechanisms. These functions involve interactions of metabolites with macromolecules. Yet, methods to systematically investigate these interactions are still scarce to date. In particular, there is a need for techniques suited to identify and characterize weak metabolite-macromolecule interactions directly in complex media such as biological fluids. Here, we introduce a method to investigate weak interactions between metabolites and macromolecules in biological fluids. Our approach is based on high-resolution NMR relaxometry and does not require any invasive procedure or separation step. We show that we can detect interactions between small and large molecules in human blood serum and quantify the size of the complex. Our work opens the way for investigations of metabolite (or other small molecules)-protein interactions in biological fluids for interactomics or pharmaceutical applications.

Multiple gene activities control complex biological processes such as cell fate specification during development and cellular reprogramming. Investigating the manifold gene functions in biological systems requires also simultaneous depletion of two or more gene activities. RNA interference-mediated knockdown (RNAi) is commonly used in Caenorhabditis elegans to assess essential genes, which otherwise lead to lethality or developmental arrest upon full knockout. RNAi application is straightforward by feeding worms with RNAi plasmid-containing bacteria. However, the general approach of mixing bacterial RNAi clones to deplete two genes simultaneously often yields poor results. To address this issue, we developed a bacterial conjugation-mediated double RNAi technique 'CONJUDOR'. It allows combining RNAi bacteria for robust double RNAi with high-throughput. To demonstrate the power of CONJUDOR for large scale double RNAi screens we conjugated RNAi against the histone chaperone gene lin-53 with more than 700 other chromatin factor genes. Thereby, we identified the Set1/MLL methyltransferase complex member RBBP-5 as a novel germ cell reprogramming barrier. Our findings demonstrate that CONJUDOR increases efficiency and versatility of RNAi screens to examine interconnected biological processes in C. elegans with high-throughput., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Label-free optical detection of biomolecules is currently limited by a lack of specificity rather than sensitivity. To exploit the much more characteristic refractive index dispersion in the mid-infrared (IR) regime, we have engineered three-dimensional IR-resonant silicon micropillar arrays (Si-MPAs) for protein sensing. By exploiting the unique hierarchical nano- and microstructured design of these Si-MPAs attained by CMOS-compatible silicon-based microfabrication processes, we achieved an optimized interrogation of surface protein binding. Based on spatially resolved surface functionalization, we demonstrate controlled three-dimensional interfacing of mammalian cells with Si-MPAs. Spatially controlled surface functionalization for site-specific protein immobilization enabled efficient targeting of soluble and membrane proteins into sensing hotspots directly from cells cultured on Si-MPAs. Protein binding to Si-MPA hotspots at submonolayer level was unambiguously detected by conventional Fourier transform IR spectroscopy. The compatibility with cost-effective CMOS-based microfabrication techniques readily allows integration of this novel IR transducer into fully fledged bioanalytical microdevices for selective and sensitive protein sensing.

Background: Activating mutations of EZH2, an epigenetic regulator, are present in approximately 20% of patients with follicular lymphoma. We investigated the activity and safety of tazemetostat, a first-in-class, oral EZH2 inhibitor, in patients with follicular lymphoma., Methods: This study was an open-label, single-arm, phase 2 trial done at 38 clinics or hospitals in France, the UK, Australia, Canada, Poland, Italy, Ukraine, Germany, and the USA. Eligible patients were adults (≥18 years) with histologically confirmed follicular lymphoma (grade 1, 2, 3a, or 3b) that had relapsed or was refractory to two or more systemic therapies, had an Eastern Cooperative Oncology Group performance status of 0-2, and had sufficient tumour tissue for central testing of EZH2 mutation status. Patients were categorised by EZH2 status: mutant (EZH2 mut ) or wild-type (EZH2 WT ). Patients received 800 mg of tazemetostat orally twice per day in continuous 28-day cycles. The primary endpoint was objective response rate based on the 2007 International Working Group criteria for non-Hodgkin lymphoma, assessed by an independent radiology committee. Activity and safety analyses were done in patients who received one dose or more of tazemetostat. This study is registered with ClinicalTrials.gov, NCT01897571, and follow-up is ongoing., Findings: Between July 9, 2015, and May 24, 2019, 99 patients (45 in the EZH2 mut cohort and 54 in the EZH2 WT cohort) were enrolled in the study. At data cutoff for the analysis (Aug 9, 2019), the median follow-up was 22·0 months (IQR 12·0-26·7) for the EZH2 mut cohort and 35·9 months (24·9-40·5) for the EZH2 WT cohort. The objective response rate was 69% (95% CI 53-82; 31 of 45 patients) in the EZH2 mut cohort and 35% (23-49; 19 of 54 patients) in the EZH2 WT cohort. Median duration of response was 10·9 months (95% CI 7·2-not estimable [NE]) in the EZH2 mut cohort and 13·0 months (5·6-NE) in the EZH2 WT cohort; median progression-free survival was 13·8 months (10·7-22·0) and 11·1 months (3·7-14·6). Among all 99 patients, treatment-related grade 3 or worse adverse events included thrombocytopenia (three [3%]), neutropenia (three [3%]), and anaemia (two [2%]). Serious treatment-related adverse events were reported in four (4%) of 99 patients. There were no treatment-related deaths., Interpretation: Tazemetostat monotherapy showed clinically meaningful, durable responses and was generally well tolerated in heavily pretreated patients with relapsed or refractory follicular lymphoma. Tazemetostat is a novel treatment for patients with follicular lymphoma., Funding: Epizyme., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Psychological aspects of labor and birth have received little attention within maternity care service planning or clinical practice. The aim of this paper is to propose a model demonstrating how neurohormonal processes, in particular oxytocinergic mechanisms, not only control the physiological aspects of labor and birth, but also contribute to the subjective psychological experiences of birth. In addition, sensory information from the uterus as well as the external environment might influence these neurohormonal processes thereby influencing the progress of labor and the experience of birth., Methodology: In this new model of childbirth, we integrated the findings from two previous systematic reviews, one on maternal plasma levels of oxytocin during physiological childbirth and one meta-synthesis of women´s subjective experiences of physiological childbirth., Findings: The neurobiological processes induced by the release of endogenous oxytocin during birth influence maternal behaviour and feelings in connection with birth in order to facilitate birth. The psychological experiences during birth may promote an optimal transition to motherhood. The spontaneous altered state of consciousness, that some women experience, may well be a hallmark of physiological childbirth in humans. The data also highlights the crucial role of one-to-one support during labor and birth. The physiological importance of social support to reduce labor stress and pain necessitates a reconsideration of many aspects of modern maternity care., Conclusion: By listening to women's experiences and by observing women during childbirth, factors that contribute to an optimized process of labor, such as the mothers' wellbeing and feelings of safety, may be identified. These observations support the integrative role of endogenous oxytocin in coordinating the neuroendocrine, psychological and physiological aspects of labor and birth, including oxytocin mediated. decrease of pain, fear and stress, support the need for midwifery one-to-one support in labour as well as the need for maternity care that optimizes the function of these neuroendocrine processes even when birth interventions are used. Women and their partners would benefit from understanding the crucial role that endogenous oxytocin plays in the psychological and neuroendocrinological process of labor., Competing Interests: The authors have declared that no competing interests exist.

Whereas our last article focused on burnout in practicing pediatric emergency medicine (PEM) physicians, this article centers on burnout in PEM fellows. Our discussion is based solely on trainee burnout literature. As graduates of pediatrics or emergency medicine residencies, PEM fellows are charged with achieving attending-level clinical expertise while continuing to cope with trainee challenges, such as limited practice autonomy, low pay, financial debt, and uncertain future employment. In this article, we discuss PEM fellow burnout and review risk and protective factors, presentation, and evidence-based interventions to mitigate it. In the absence of PEM fellow-specific literature, we share pediatrics and emergency medicine residency data.This article is dedicated to the trainees we have lost to suicide. We miss you.

Diffusion controlled chemical reactions are usually observed in three dimensional media. In contrast, planar bimolecular reactions taking place between reagents adsorbed at a soft interface are two-dimensional and therefore cannot be studied within the same formalism. Indeed, soft interfaces allow the adsorbed species to freely diffuse in a liquid-like manner. Here, we present the first experimental observation of a diffusion-controlled reaction in an environment that is planar at the ångström scale. By means of time-resolved surface second harmonic generation, an inherently surface sensitive technique, we observed that the kinetics of the diffusion of the reagents in the plane decreases as the surface concentration of adsorbed species increases. This is of course not the case for bulk reactions where the rates always increase with the reactant concentration. Such changes in the kinetics regime were rationalised as the evolution from a regular 2D free diffusion regime to a geometry-controlled scheme., (This journal is © The Royal Society of Chemistry 2019.)

The predictors of social closeness toward refugees are rarely examined. In this study (N = 337), higher cultural intelligence (CQ) and higher empathy were defined as predictors of higher social closeness (lower social distance [the Social Distance Scale] and warmer feelings [the Feeling Thermometer]) toward refugees from Syria. This is the target group of prejudice and intensive coverage in the European mass media. The obtained results indicated that other-oriented empathy (empathic concern and perspective taking) and the motivational CQ predicted higher social closeness and warmer feelings toward refugees from Syria. Empathic personal distress predicted lower social closeness and colder feelings toward this group. Motivational CQ consistently served as the mediator of the relationship between empathy dimensions and social closeness toward Syrian refugees. Our findings reveal the previously unexplored correlations between empathy dimensions and cultural intelligence factors, including the mediational effects in predicting social closeness toward Syrian refugees., (© 2019 Wiley Periodicals, Inc.)

Chromatin regulators play important roles in the safeguarding of cell identities by opposing the induction of ectopic cell fates and, thereby, preventing forced conversion of cell identities by reprogramming approaches. Our knowledge of chromatin regulators acting as reprogramming barriers in living organisms needs improvement as most studies use tissue culture. We used Caenorhabditis elegans as an in vivo gene discovery model and automated solid-phase RNA interference screening, by which we identified 10 chromatin-regulating factors that protect cells against ectopic fate induction. Specifically, the chromodomain protein MRG-1 safeguards germ cells against conversion into neurons. MRG-1 is the ortholog of mammalian MRG15 (MORF-related gene on chromosome 15) and is required during germline development in C. elegans However, MRG-1's function as a barrier for germ cell reprogramming has not been revealed previously. Here, we further provide protein-protein and genome interactions of MRG-1 to characterize its molecular functions. Conserved chromatin regulators may have similar functions in higher organisms, and therefore, understanding cell fate protection in C. elegans may also help to facilitate reprogramming of human cells., (Copyright © 2019 Hajduskova et al.)

Objective: To synthesise qualitative studies on women's psychological experiences of physiological childbirth., Design: Meta-synthesis., Methods: Studies exploring women's psychological experiences of physiological birth using qualitative methods were eligible. The research group searched the following databases: MEDLINE, CINAHL, PsycINFO, PsycARTICLES, SocINDEX and Psychology and Behavioural Sciences Collection. We contacted the key authors searched reference lists of the collected articles. Quality assessment was done independently using the Critical Appraisal Skills Programme (CASP) checklist. Studies were synthesised using techniques of meta-ethnography., Results: Eight studies involving 94 women were included. Three third order interpretations were identified: 'maintaining self-confidence in early labour', 'withdrawing within as labour intensifies' and 'the uniqueness of the birth experience'. Using the first, second and third order interpretations, a line of argument developed that demonstrated 'the empowering journey of giving birth' encompassing the various emotions, thoughts and behaviours that women experience during birth., Conclusion: Giving birth physiologically is an intense and transformative psychological experience that generates a sense of empowerment. The benefits of this process can be maximised through physical, emotional and social support for women, enhancing their belief in their ability to birth and not disturbing physiology unless it is necessary. Healthcare professionals need to take cognisance of the empowering effects of the psychological experience of physiological childbirth. Further research to validate the results from this study is necessary., Prospero Registration Number: CRD42016037072., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Expression of the NPM1 gene, encoding nucleophosmin, is upregulated in cancers. Although more than ten NPM1 transcripts are known, the reports were usually limited to one predominant transcript. In leukemia, the NPM1 expression has not been widely studied so far. In acute myeloid leukemia (AML), the mutational status of the gene seems to play a pivotal role in carcinogenesis. Therefore, the aim of the study was to quantify alternative NPM1 transcripts in two types of acute leukemia, AML and ALL (acute lymphoblastic leukemia)., Methods: Using droplet digital PCR, we analyzed the levels of three protein-coding NPM1 transcripts in 66 samples collected from AML and ALL patients and 16 control samples. Using RNA-seq, we detected 8 additional NPM1 transcripts, including non-coding splice variants with retained introns. For data analysis, Welch two sample t-test, Pearson's correlation and Kaplan-Meier analysis were applied., Results: The levels of the particular NPM1 transcripts were significantly different but highly correlated with each other in both leukemia and control samples. Transcript NPM1.1, encoding the longest protein (294 aa), had the highest level of accumulation and was one of the most abundant transcripts in the cell. Comparing to NPM1.1, the levels of the NPM1.2 and NPM1.3 transcripts, encoding a 265-aa and 259-aa proteins, were 30 and 3 times lower, respectively. All three NPM1 transcripts were proportionally upregulated in both types of leukemia compared to control samples. In AML, the levels of NPM1 transcripts decreased in complete remission and increased again with relapse of the disease. Low levels of NPM1.1 and NPM1.3 were associated with better prognosis. The contribution of non-coding transcripts to the total level of NPM1 gene seemed to be marginal, except for one short 5-end transcript accumulated at high levels in AML and control cells. Aberrant proportions of particular NPM1 splice variants could be linked to abnormal expression of genes encoding alternative splicing factors., Conclusions: The levels of the studied NPM1 transcripts were different but highly correlated with each other. Their upregulation in AML and ALL, decrease after therapy and association with patient outcome suggests the involvement of elevated NPM1 expression in the acute leukemia pathogenesis.

Objective: Individual well care (IWC) is the standard delivery model for well-child care in the United States. Alternative models, such as group well care (GWC), may create opportunities to enhance care for babies. The purpose of this study was to evaluate parents' perceptions of social/wellness benefits and system challenges of IWC and GWC., Methods: Since 2014, we have provided both IWC and GWC at an urban academic practice serving a low-income minority community. We conducted a mixed method study involving surveys and 18 focus groups (11 IWC groups, n = 32 parents; 7 GWC groups, n = 33 parents). Parents completed surveys before convening focus group discussions. Survey results were analyzed using independent t tests; focus groups were digitally recorded, transcribed, and analyzed to identify themes., Results: Both groups had similar demographics: parents were mostly female (91%) and black (>80%); about half had incomes < $20,000. Parents' mean age was 27 years; children's mean age was 11 months. There were no significant differences in overall scores measuring trust in physicians, parent empowerment, or stress. IWC parents' themes highlighted ways to improve care delivery, while GWC parents highlighted both satisfaction with care delivery and social/wellness benefits. GWC parents strongly endorsed this model and reported unique benefits, such as garnering social support and learning from other parents., Conclusions: Parents receiving both models of care identified ways to improve primary care delivery. Given some of the benefits reported by GWC parents, this model may provide the means to enhance resilience in parents and children in low-income communities., (Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Understanding the structure and dynamics of highly diverse tropical forests is challenging. Here we investigate the factors that drive the spatio-temporal variation of local tree numbers and species richness in a tropical forest (including 1250 plots of 20 × 20 m 2 ). To this end, we use a series of dynamic models that are built around the local spatial variation of mortality and recruitment rates, and ask which combination of processes can explain the observed spatial and temporal variation in tree and species numbers. We find that processes not included in classical neutral theory are needed to explain these fundamental patterns of the observed local forest dynamics. We identified a large spatio-temporal variability in the local number of recruits as the main missing mechanism, whereas variability of mortality rates contributed to a lesser extent. We also found that local tree numbers stabilize at typical values which can be explained by a simple analytical model. Our study emphasized the importance of spatio-temporal variability in recruitment beyond demographic stochasticity for explaining the local heterogeneity of tropical forests., (© 2017 The Author(s).)

Mutations in the Pejvakin ( PJVK ) gene are thought to cause auditory neuropathy and hearing loss of cochlear origin by affecting noise-induced peroxisome proliferation in auditory hair cells and neurons. Here we demonstrate that loss of pejvakin in hair cells, but not in neurons, causes profound hearing loss and outer hair cell degeneration in mice. Pejvakin binds to and colocalizes with the rootlet component TRIOBP at the base of stereocilia in injectoporated hair cells, a pattern that is disrupted by deafness-associated PJVK mutations. Hair cells of pejvakin-deficient mice develop normal rootlets, but hair bundle morphology and mechanotransduction are affected before the onset of hearing. Some mechanotransducing shorter row stereocilia are missing, whereas the remaining ones exhibit overextended tips and a greater variability in height and width. Unlike previous studies of Pjvk alleles with neuronal dysfunction, our findings reveal a cell-autonomous role of pejvakin in maintaining stereocilia architecture that is critical for hair cell function. SIGNIFICANCE STATEMENT Two missense mutations in the Pejvakin ( PJVK or DFNB59 ) gene were first identified in patients with audiological hallmarks of auditory neuropathy spectrum disorder, whereas all other PJVK alleles cause hearing loss of cochlear origin. These findings suggest that complex pathogenetic mechanisms underlie human deafness DFNB59. In contrast to recent studies, we demonstrate that pejvakin in auditory neurons is not essential for normal hearing in mice. Moreover, pejvakin localizes to stereociliary rootlets in hair cells and is required for stereocilia maintenance and mechanosensory function of the hair bundle. Delineating the site of the lesion and the mechanisms underlying DFNB59 will allow clinicians to predict the efficacy of different therapeutic approaches, such as determining compatibility for cochlear implants., (Copyright © 2017 the authors 0270-6474/17/373447-18$15.00/0.)

Mutations in the Pejvakin (Pjvk) gene cause autosomal recessive hearing loss DFNB59 with audiological features of auditory neuropathy spectrum disorder (ANSD) or cochlear dysfunction. The precise mechanisms underlying the variable clinical phenotypes of DFNB59 remain unclear. Here, we demonstrate that mice with conditional ablation of the Pjvk gene in all sensory hair cells or only in outer hair cells (OHCs) show similar auditory phenotypes with early-onset profound hearing loss. By contrast, loss of Pjvk in adult OHCs causes a slowly progressive hearing loss associated with OHC degeneration and delayed loss of inner hair cells (IHCs), indicating a primary role for pejvakin in regulating OHC function and survival. Consistent with this model, synaptic transmission at the IHC ribbon synapse is largely unaffected in sirtaki mice that carry a C-terminal deletion mutation in Pjvk. Using the C-terminal domain of pejvakin as bait, we identified in a cochlear cDNA library ROCK2, an effector for the small GTPase Rho, and the scaffold protein IQGAP1, involved in modulating actin dynamics. Both ROCK2 and IQGAP1 associate via their coiled-coil domains with pejvakin. We conclude that pejvakin is required to sustain OHC activity and survival in a cell-autonomous manner likely involving regulation of Rho signaling., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

The NPM1 gene encodes nucleophosmin, a protein involved in multiple cell functions and carcinogenesis. Mutation of the NPM1 gene, causing delocalization of the protein, is the most frequent genetic lesion in acute myeloid leukemia (AML); it is considered a founder event in AML pathogenesis and serves as a favorable prognostic marker. Moreover, in solid tumors and some leukemia cell lines, overexpression of the NPM1 gene is commonly observed. Therefore, the purpose of this study was to develop a new method for the detection of NPM1 mutations and the simultaneous analysis of copy number alterations (CNAs), which may underlie NPM1 gene expression deregulation. To address both of the issues, we applied a strategy based on multiplex ligation-dependent probe amplification (MLPA). A designed NPM1mut+ assay enables the detection of three of the most frequent NPM1 mutations: A, B and D. The accuracy of the assay was tested using a group of 83 samples from Polish patients with AML and other blood-proliferative disorders. To verify the results, we employed traditional Sanger sequencing and next-generation transcriptome sequencing. With the use of the NPM1mut+ assay, we detected mutations A, D and B in 14, 1 and 0 of the analyzed samples, respectively. All of these mutations were confirmed by complementary sequencing approaches, proving the 100% specificity and sensitivity of the proposed test. The performed sequencing analysis allowed the identification of two additional rare mutations (I and ZE). All of the mutations were identified exclusively in AML cases, accounting for 25% of those cases. We did not observe any CNAs (amplifications) of the NPM1 gene in the studied samples, either with or without the mutation. The presented method is simple, reliable and cost-effective. It can be easily introduced into clinical practice or developed to target both less-frequent mutations in the NPM1 gene and other cancer-related genes., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Tropical forests are highly diverse ecosystems, but within such forests there can be large patches dominated by a single tree species. The myriad presumed mechanisms that lead to the emergence of such monodominant areas is currently the subject of intensive research. We used the most generic of these mechanisms, large seed mass and low dispersal ability of the monodominant species, in a spatially explicit model. The model represents seven identical species with long-distance dispersal of small seeds, competing with one potentially monodominant species with short-distance dispersal of large seeds. Monodominant patches emerged and persisted only for a narrow range of species traits; these results have the characteristic features of phase transitions. Additional mechanisms may explain monodominance in different ecological contexts, but our results suggest that percolation-like phenomena and phase transitions might be pervasive in this type of system., (© 2016 The Author(s).)

Disordered protein ubiquitination has been linked to neurodegenerative disease, yet its role in inner ear homeostasis and hearing loss is essentially unknown. Here we show that progressive hearing loss in the ethylnitrosourea-generated mambo mouse line is caused by a mutation in Usp53, a member of the deubiquitinating enzyme family. USP53 contains a catalytically inactive ubiquitin-specific protease domain and is expressed in cochlear hair cells and a subset of supporting cells. Although hair cell differentiation is unaffected in mambo mice, outer hair cells degenerate rapidly after the first postnatal week. USP53 colocalizes and interacts with the tight junction scaffolding proteins TJP1 and TJP2 in polarized epithelial cells, suggesting that USP53 is part of the tight junction complex. The barrier properties of tight junctions of the stria vascularis appeared intact in a biotin tracer assay, but the endocochlear potential is reduced in adult mambo mice. Hair cell degeneration in mambo mice precedes endocochlear potential decline and is rescued in cochlear organotypic cultures in low potassium milieu, indicating that hair cell loss is triggered by extracellular factors. Remarkably, heterozygous mambo mice show increased susceptibility to noise injury at high frequencies. We conclude that USP53 is a novel tight junction-associated protein that is essential for the survival of auditory hair cells and normal hearing in mice, possibly by modulating the barrier properties and mechanical stability of tight junctions., Significance Statement: Hereditary hearing loss is extremely prevalent in the human population, but many genes linked to hearing loss remain to be discovered. Forward genetics screens in mice have facilitated the identification of genes involved in sensory perception and provided valuable animal models for hearing loss in humans. This involves introducing random mutations in mice, screening the mice for hearing defects, and mapping the causative mutation. Here, we have identified a mutation in the Usp53 gene that causes progressive hearing loss in the mambo mouse line. We demonstrate that USP53 is a catalytically inactive deubiquitinating enzyme and a novel component of tight junctions that is necessary for sensory hair cell survival and inner ear homeostasis., (Copyright © 2015 the authors 0270-6474/15/3515582-17$15.00/0.)

Breastfeeding supports the formation of an emotional bond between mothers and their children. The feeding method is associated with both the child's temperament and the mother's perception of herself and the child. Therefore, the present study focuses on the feeding method, mothers' reaction during feeding, and infants' temperament traits. Ninety-eight mothers with children aged 3 to 5 months participated in the study. Children were assessed with the Children Development Scale (A. Matczak et al., 2007) to measure their temperament. Mothers completed the Mother and Baby Scale (D. Wolke & I. St James-Roberts, 1987, as cited in T.B. Brazelton & K. Nugent, 1995), which measures mothers' evaluation of their children's behaviors during feeding and their overall experiences with their children's care. The results show that breastfed newborns, as compared to bottle-fed newborns, demonstrate higher vigor, which includes activity and the intensity of reaction. Bottle-fed children demonstrate higher regularity than do breastfed children. Mothers who bottle-feed their children perceive themselves to be less confident in the feeding domain than do mothers who breastfeed. Our results indicate that children's temperament might be an important factor in the decision regarding the feeding method. The study supports the idea of promoting knowledge of children's behaviors during feeding among mothers even before their children are born, such as during antenatal classes., (© 2015 Michigan Association for Infant Mental Health.)