Introduction—Grand Challenges and small steps

This collection addresses two different audiences: 1) historians and philosophers of the life sciences reflecting on collaborations across disciplines, especially as regards defining and addressing Grand Challenges; 2) researchers and other stakeholders involved in cross-disciplinary collaborations aimed at tackling Grand Challenges in the life and medical sciences. The essays collected here offer ideas and resources both for the study and for the practice of goal-driven cross-disciplinary research in the life and medical sciences. We organise this introduction in three sections. The first section provides some background and context. The second motivates our take on this topic and then outlines the central ideas of each paper. The third section highlights the specificity and significance of this approach by considering: a) how this collection departs from existing literature on inter- and transdisciplinarity, b) what is characteristic about this approach, and c) what role this suggests for the history and philosophy of the life sciences in addressing Grand Challenges

Immunohistochemical Distribution of Serotonin Transporter (SERT) in the Optic Lobe of the Honeybee, Apis mellifera

Visual information is processed in the optic lobes, which consist of three retinotopic neuropils. These are the lamina, the medulla and the lobula. Biogenic amines play a crucial role in the control of insect responsiveness, and serotonin is clearly related to aggressiveness in invertebrates. Previous studies suggest that serotonin modulates aggression-related behaviours, possibly via alterations in optic lobe activity. The aim of this investigation was to immunohistochemically localize the distribution of serotonin transporter (SERT) in the optic lobe of moderate, docile and aggressive worker honeybees. SERT-immunoreactive fibres showed a wide distribution in the lamina, medulla and lobula; interestingly, the highest percentage of SERT immunoreactivity was observed across all the visual neuropils of the docile group. Although future research is needed to determine the relationship between the distribution of serotonin fibres in the honeybee brain and aggressive behaviours, our immunohistochemical study provides an anatomical basis supporting the role of serotonin in aggressive behaviour in the honeybee

Harvesting the promise of AOPs: An assessment and recommendations

The Adverse Outcome Pathway (AOP) concept is a knowledge assembly and communication tool to facilitate the transparent translation of mechanistic information into outcomes meaningful to the regulatory assessment of chemicals. The AOP framework and associated knowledgebases (KBs) have received significant attention and use in the regulatory toxicology community. However, it is increasingly apparent that the potential stakeholder community for the AOP concept and AOP KBs is broader than scientists and regulators directly involved in chemical safety assessment. In this paper we identify and describe those stakeholders who currently—or in the future—could benefit from the application of the AOP framework and knowledge to specific problems. We also summarize the challenges faced in implementing pathway-based approaches such as the AOP framework in biological sciences, and provide a series of recommendations to meet critical needs to ensure further progression of the framework as a useful, sustainable and dependable tool supporting assessments of both human health and the environment. Although the AOP concept has the potential to significantly impact the organization and interpretation of biological information in a variety of disciplines/applications, this promise can only be fully realized through the active engagement of, and input from multiple stakeholders, requiring multi-pronged substantive long-term planning an d strategies

Inteligencia emocional y calidad de vida en período de aislamiento social, preventivo y obligatorio durante la pandemia por COVID-19

Our goal is to describe the levels of the variables Emotional Intelligence (EI) and Quality of Life (QoL) in subjects affected by the context of Social, Preventive and Mandatory Isolation decreed on March 20 in Argentina during the COVID-19 pandemic, evaluate if there are significant relationships between them and analyze if they present differences based on sociodemographic variables such as: age and gender. We worked with a sample made up of 923 female and male people over 18 years of age from the general population. An ad-hoc sociodemographic questionnaire, the Trait Meta-Mood Scale (TMMS-24) instrument, and the Multicultural Quality of Life Index (MQLI) were used for data collection. The sample was contacted online from March 29 to July 6, 2020. The results showed that the correlation between the variable IE and CV was significant. The dimensions of these variables presented weak relationship strength with each other except Emotional Attention that only significantly correlated with a strong link strength with the variables Spiritual Fullness and Social Support as well as with Interpersonal Functioning, this time with moderate link strength. The levels of the CV variable are described as good in most of the subjects in the sample. EI levels are described as adequate for both genders in almost all subscales, presenting a difference for the gender in Emotional Clarity, resulting little for the male and adequate for the female, thus corroborating the hypotheses raised. Regarding the link between the EI and QOL variables based on the sociodemographic variables, significant differences were obtained in groups, being those between 71 and 80 years old, who do not consume psychoactive substances underwritten by a professional, and those who have a recreational containment network who obtained higher scores. In conclusion the results suggest that, although associations were found, longitudinal studies are necessary to consider the different phases of quarantineSe propuso describir los niveles de las variables inteligencia emocional (IE) y calidad de vida (CV) en sujetos afectados por el contexto del aislamiento social, preventivo y obligatorio en Argentina a raíz de la pandemia por COVID-19, evaluar si existen relaciones significativas entre ellas y analizar si presentan diferencias en función de variables sociodemográficas. Se trabajó con una muestra conformada por 923 personas de géneros femenino y masculino, mayores de 18 años, de población general. Para el relevamiento de datos se utilizó un cuestionario sociodemográfico confeccionado ad hoc, la Trait Meta-Mood Scale (TMMS-24) —una escala para evaluar la inteligencia emocional percibida— y el Multicultural Quality of Life Index (MQLI), o índice multicultural de calidad de vida. La muestra fue contactada virtualmente entre el 29 de marzo y el 6 de julio de 2020. Los resultados arrojaron que la correlación entre las variables IE y CV fue significativa. Las dimensiones de dichas variables presentaron una fuerza de relación débil entre sí, exceptuando atención emocional, que correlacionó con una fuerza de vínculo fuerte con plenitud espiritual y apoyo social-emocional, y moderadamente con funcionamiento interpersonal. Los niveles de la variable CV se describen como buenos para la mayoría de los sujetos de la muestra. Los niveles de IE se describen como adecuados para ambos géneros en casi todas las subescalas exceptuando la dimensión claridad emocional, resultando poca para el masculino y adecuada para el femenino. Respecto al vínculo de IE y CV en función de variables sociodemográficas, se obtuvieron diferencias significativas entre grupos; y el grupo etario 71-80 años, quienes no consumen sustancias psicoactivas suscriptas por un profesional y los que poseen una red de contención recreativa obtuvieron mayores puntuaciones. En conclusión, si bien se encontraron asociaciones, los resultados sugieren la necesidad de estudios longitudinales que contemplen las diferentes fases de la cuarenten

Regulation during the second year: Executive function and emotion regulation links to joint attention, temperament, and social vulnerability in a Latin American sample

© 2019 Gago Galvagno, De Grandis, Clerici, Mustaca, Miller and Elgier. Although a growing body of work has established developing regulatory abilities during the second year of life, more work is needed to better understand factors that influence this emerging control. The purpose of the present study was to examine regulation capacities in executive functions (i.e., EF or cognitive control) and emotion regulation (i.e., ER or control focused on modulating negative and sustaining positive emotions) in a Latin American sample, with a focus on how joint attention, social vulnerability, and temperament contribute to performance. Sixty Latin American dyads of mothers and children aged 18 to 24 months completed several EF tasks, a Still-Face Paradigm (SFP) to examine ER (Weinberg et al., 2008), and the Early Social Communication Scale to measure joint attention (Mundy et al., 2003). Parents completed the Early Childhood Behavior Questionnaire Very Short Form to measure temperament (ECBQ-VS, Putnam et al., 2010) and the Social Economic Level Scale (SES) from INDEC (2000). Results revealed the typical responses expected for toddlers of this age in these EF tasks and in the SFP. Also, we found associations between EF and ER and between non-verbal communication related to monitoring infants\u27 attention to objects (i.e., responding to joint attention) and initiation of pointing (e.g., pointing and showing of an object while the child alternates his gaze to an adult) with EF. Regarding social factors, family differences and type of housing contribute to regulation. For temperament, effortful control was associated with both regulatory capacities. Finally, only age predicted EF. These results suggest that many patterns regarding the development of these abilities are duplicated in the first months of life in a Latin American sample while further highlighting the importance of considering how the environment and the individual characteristics of infants may associate to these regulatory abilities, which is particularly relevant to developing public policies to promote their optimal development

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification

Two novel missense mutations in the myelin protein zero gene causes Charcot-Marie-Tooth type 2 and Déjérine-Sottas syndrome

<p>Abstract</p> <p>Background</p> <p>The Charcot-Marie-Tooth (CMT) phenotype caused by mutation in the <it>myelin protein zero (MPZ) </it>gene varies considerably, from early onset and severe forms to late onset and milder forms. The mechanism is not well understood. The myelin protein zero (P₀) mediates adhesion in the spiral wraps of the Schwann cell's myelin sheath. The crystalline structure of the extracellular domain of the myelin protein zero (P₀ex) is known, while the transmembrane and intracellular structure is unknown.</p> <p>Findings</p> <p>One novel missense mutation caused a milder late onset CMT type 2, while the second missense mutation caused a severe early onset phenotype compatible with Déjérine-Sottas syndrome.</p> <p>Conclusions</p> <p>The phenotypic variation caused by different missense mutations in the <it>MPZ </it>gene is likely caused by different conformational changes of the MPZ protein which affects the functional tetramers. Severe changes of the MPZ protein cause dysfunctional tetramers and predominantly uncompacted myelin, i.e. the severe phenotypes congenital hypomyelinating neuropathy and Déjérine-Sottas syndrome, while milder changes cause the phenotypes CMT type 1 and 2.</p

Necdin, a Negative Growth Regulator, Is a Novel STAT3 Target Gene Down-Regulated in Human Cancer

Cytokine and growth factor signaling pathways involving STAT3 are frequently constitutively activated in many human primary tumors, and are known for the transcriptional role they play in controlling cell growth and cell cycle progression. However, the extent of STAT3's reach on transcriptional control of the genome as a whole remains an important question. We predicted that this persistent STAT3 signaling affects a wide variety of cellular functions, many of which still remain to be characterized. We took a broad approach to identify novel STAT3 regulated genes by examining changes in the genome-wide gene expression profile by microarray, using cells expressing constitutively-activated STAT3. Using computational analysis, we were able to define the gene expression profiles of cells containing activated STAT3 and identify candidate target genes with a wide range of biological functions. Among these genes we identified Necdin, a negative growth regulator, as a novel STAT3 target gene, whose expression is down-regulated at the mRNA and protein levels when STAT3 is constitutively active. This repression is STAT3 dependent, since inhibition of STAT3 using siRNA restores Necdin expression. A STAT3 DNA-binding site was identified in the Necdin promoter and both EMSA and chromatin immunoprecipitation confirm binding of STAT3 to this region. Necdin expression has previously been shown to be down-regulated in a melanoma and a drug-resistant ovarian cancer cell line. Further analysis of Necdin expression demonstrated repression in a STAT3-dependent manner in human melanoma, prostate and breast cancer cell lines. These results suggest that STAT3 coordinates expression of genes involved in multiple metabolic and biosynthetic pathways, integrating signals that lead to global transcriptional changes and oncogenesis. STAT3 may exert its oncogenic effect by up-regulating transcription of genes involved in promoting growth and proliferation, but also by down-regulating expression of negative regulators of the same cellular processes, such as Necdin