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Objectives Globally, drug-resistant tuberculosis (DR-TB) is the leading cause of death globally related to antimicrobial resistance, affecting 500,000 emergent cases annually. In 2018, the first United Nations High-Level Meeting (UNHLM) on tuberculosis declared DR-TB a global public health priority. Bold country targets were established for 2018–2022. This study reviews the DR-TB situation in 2018, and the UNHLM target accomplishments in 10 high-burden countries (HBCs). Methods An ecological descriptive analysis of the top 10 DR-TB HBCs (Bangladesh, China, India, Indonesia, Myanmar, Nigeria, Pakistan, Philippines, Russian Federation, and South Africa), which share 70% of the global DR-TB burden, was undertaken, complemented by a cascade-of-care analysis and a survey gathering additional information on key advances and setbacks 2 years after the UNHLM declaration. Results Most countries are showing historic advances and are on track for the 2018 and 2019 targets. However, according to the cascade-of-care, none of the countries are capable of providing effective care for 50% of the estimated patients. Increasing levels of fluoroquinolone resistance and access to timely susceptibility testing can jeopardize ongoing adoption of shorter, all-oral treatment regimens. The programmatic management of DR-TB in children remains minimal. Achievements for 2020 and beyond may be affected significantly by the coronavirus disease 2019 (COVID-19) pandemic. Conclusion Triggered by the COVID-19 pandemic, there is a global risk of recoil in DR-TB care with long-term consequences in terms of deaths, suffering and wider transmission. Investment to support DR-TB services is more important now than ever to meet the aspirations of the UNHLM declaration.

A striking feature of the nervous system pertains to the appearance of different neural cell subtypes at different axial levels. Studies in the Drosophila central nervous system reveal that one mechanism underlying such segmental differences pertains to the segment-specific removal of cells by programmed cell death (PCD). One group of genes involved in segment-specific PCD is the Hox homeotic genes. However, while segment-specific PCD is highly precise, Hox gene expression is evident in gradients, raising the issue of how the Hox gene function is precisely gated to trigger PCD in specific segments at the outer limits of Hox expression. The Drosophila Va neurons are initially generated in all nerve cord segments but removed by PCD in posterior segments. Va PCD is triggered by the posteriorly expressed Hox gene Abdominal-B (Abd-B). However, Va PCD is highly reproducible despite exceedingly weak Abd-B expression in the anterior frontiers of its expression. Here, we found that the transcriptional cofactor Dachshund supports Abd-B-mediated PCD in its anterior domain. In vivo bimolecular fluorescence complementation analysis lends support to the idea that the Dachshund/Abd-B interplay may involve physical interactions. These findings provide an example of how combinatorial codes of transcription factors ensure precision in Hox-mediated PCD in specific segments at the outer limits of Hox expression, Ministerio de Ciencia y Educación, Grant/Award Number: PID2019-110952GB-I00

The modulation of the host’s metabolism to protect tissue from damage induces tolerance to infections increasing survival. Here, we examined the role of the thyroid hormones, key metabolic regulators, in the outcome of malaria. Hypothyroidism confers protection to experimental cerebral malaria by a disease tolerance mechanism. Hypothyroid mice display increased survival after infection with Plasmodium berghei ANKA, diminishing intracranial pressure and brain damage, without altering pathogen burden, blood-brain barrier disruption, or immune cell infiltration. This protection is reversed by treatment with a Sirtuin 1 inhibitor, while treatment of euthyroid mice with a Sirtuin 1 activator induces tolerance and reduces intracranial pressure and lethality. This indicates that thyroid hormones and Sirtuin 1 are previously unknown targets for cerebral malaria treatment, a major killer of children in endemic malaria areas., This work was funded by grants SAF2017-83289-R to S.A. and A.A., SAF2017-90604REDT to A.A. supported by the The European Regional Development Fund (FEDER) and BIO2016-77430-R to J.M.B. from the Ministerio de Economía y Competitividad; B2017/BMD-3724 to S.A. and A.A. from the Comunidad de Madrid; and CIBERONC CB/16/00228 to A.A. from the Instituto de Salud Carlos III.

A prominent aspect of most, if not all, central nervous systems (CNSs) is that anterior regions (brain) are larger than posterior ones (spinal cord). Studies in Drosophila and mouse have revealed that Polycomb Repressor Complex 2 (PRC2), a protein complex responsible for applying key repressive histone modifications, acts by several mechanisms to promote anterior CNS expansion. However, it is unclear what the full spectrum of PRC2 action is during embryonic CNS development and how PRC2 intersects with the epigenetic landscape. We removed PRC2 function from the developing mouse CNS, by mutating the key gene Eed, and generated spatio-temporal transcriptomic data. To decode the role of PRC2, we developed a method that incorporates standard statistical analyses with probabilistic deep learning to integrate the transcriptomic response to PRC2 inactivation with epigenetic data. This multi-variate analysis corroborates the central involvement of PRC2 in anterior CNS expansion, and also identifies several unanticipated cohorts of genes, such as proliferation and immune response genes. Furthermore, the analysis reveals specific profiles of regulation via PRC2 upon these gene cohorts. These findings uncover a differential logic for the role of PRC2 upon functionally distinct gene cohorts that drive CNS anterior expansion. To support the analysis of emerging multi-modal datasets, we provide a novel bioinformatics package that integrates transcriptomic and epigenetic datasets to identify regulatory underpinnings of heterogeneous biological processes. Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission [621-2013-5258]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [KAW2011.0165, KAW2012.0101]; Swedish Cancer Foundation [140780, 150663]; University of QueenslandUniversity of Queensland; Australian Government Research Training ProgramAustralian Government

OBJECTIVES: To study the nutritional value of cocoa shell, analyzing the chemical composition and functional properties as antioxidant, hypoglycemic and hypocholesterolemic effects, as well as validate the safety of cocoa shell as a sustainable food ingredient. METHODS: Proximate composition was determined following the AOAC methods. Soluble and insoluble fractions of dietary fiber (DF) were determined using enzymatic-gravimetric and chemical methods. The phenolic profile was analyzed by UPLC-MS/MS and antioxidant properties were tested using ABTS. Furthermore, physicochemical, hypoglycemic, and hypocholesterolemic properties were assessed in vitro. Acute and subchronic oral toxicity experiments were performed following OECD Guidelines 452 and 408 (5 male and 5 female C57BL/6 mice per group, vehicle/cocoa shell) to assess the food safety of cocoa shell flours. RESULTS: Cocoa shell was composed of carbohydrates (62%), proteins (16%), and fat (2%). DF represents 59%, being the insoluble dietary fiber (IDF) the main fraction (82%). IDF fraction was constituted by lignin (58%) and polysaccharides (42%); cellulose was inferred as the main polysaccharide of IDF, followed by hemicelluloses (arabinans and galactans). High content of phenolic compounds (33.7 mg/g) was shown, being a significant phenolic fraction (51%) bound to DF, which confers cocoa shell its antioxidant potential (73.1 mg Trolox eq/g). The main phenolics were protocatechuic acid, (−)-epicatechin, and (+)-catechin. Cocoa shell exhibited adequate water and oil holding properties to be included in food matrices. During in vitro digestion, starch hydrolysis and dialyzed glucose diminished (34 and 13%, respectively) due to α-amylase inhibition (18%) and glucose adsorption (31%). Cocoa shell also inhibited cholesterol and bile salts absorption (72 and 70%, respectively). The intake of acute (2000 mg/kg) and subcronical (1000 mg/kg) doses of the ingredient did not cause significant lesions in selected isolated vital organs (liver, spleen, and kidney) nor changes in histological parameters, ensuring the safety of this sustainable food ingredient. CONCLUSIONS: Results validate the use of cocoa shell as an antioxidant dietary fiber ingredient, being a safe potential candidate to be incorporated in the development of foods for specific health uses. FUNDING SOURCES: Ministry of Science and Innovation.

Despite recent advances and well-known treatment options, cure rates for resistant tuberculosis (TB) cases remain extraordinarily low. We present in first person the case of a patient who suffered from TB for over 7 years, and travelled to four countries in search of a cure. This experience shows how resistance patterns worsen under poor programme conditions and illustrates many of the obstacles faced by patients to obtain appropriate care: late diagnosis, lack of experienced care capacity and drug availability, and absence of psychosocial support during toxic and lengthy regimens. In addition to new tools, patient-centred systems are needed to tackle the drug-resistant TB epidemic.

Item does not contain fulltext BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0.15, 95% CI 0.11 to 0.18), levofloxacin (0.15, 0.13 to 0.18), carbapenems (0.14, 0.06 to 0.21), moxifloxacin (0.11, 0.08 to 0.14), bedaquiline (0.10, 0.05 to 0.14), and clofazimine (0.06, 0.01 to 0.10). There was a significant association between reduced mortality and use of linezolid (-0.20, -0.23 to -0.16), levofloxacin (-0.06, -0.09 to -0.04), moxifloxacin (-0.07, -0.10 to -0.04), or bedaquiline (-0.14, -0.19 to -0.10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I(2) method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Despite being considered one of the major infectious diseases in terms of mortality and morbidity, tuberculosis (TB) has not been among the priorities of the scientific community and pharmaceutical...

During embryonic development, a number of genetic cues act to generate neuronal diversity. While intrinsic transcriptional cascades are well-known to control neuronal sub-type cell fate, the target cells can also provide critical input to specific neuronal cell fates. Such signals, denoted retrograde signals, are known to provide critical survival cues for neurons, but have also been found to trigger terminal differentiation of neurons. One salient example of such target-derived instructive signals pertains to the specification of the Drosophila FMRFamide neuropeptide neurons, the Tv4 neurons of the ventral nerve cord. Tv4 neurons receive a BMP signal from their target cells, which acts as the final trigger to activate the FMRFa gene. A recent FMRFa-eGFP genetic screen identified several genes involved in Tv4 specification, two of which encode components of the U5 subunit of the spliceosome: brr2 (l(3)72Ab) and Prp8. In this study, we focus on the role of RNA processing during target- derived signaling. We found that brr2 and Prp8 play crucial roles in controlling the expression of the FMRFa neuropeptide specifically in six neurons of the VNC (Tv4 neurons). Detailed analysis of brr2 revealed that this control is executed by two independent mechanisms, both of which are required for the activation of the BMP retrograde signaling pathway in Tv4 neurons: (1) Proper axonal pathfinding to the target tissue in order to receive the BMP ligand. (2) Proper RNA splicing of two genes in the BMP pathway: the thickveins (tkv) gene, encoding a BMP receptor subunit, and the Medea gene, encoding a co-Smad. These results reveal involvement of specific RNA processing in diversifying neuronal identity within the central nervous system, The study was funded by Ministerio de Economía y competitividad (http://www.mineco. gob.es/portal/site/mineco/), reference: BFU2016- 78327-P (to JB-S); Swedish Research Council (https://www.vr.se/inenglish.4. 12fff4451215cbd83e4800015152.html), reference: 621-2010-5214 (to ST); Knut and Alice Wallenberg Foundation (https://kaw.wallenberg.org), reference KAW2011.0165 (to ST); Swedish Cancer Foundation (https://www.cancerfonden.se/om- cancerfonden/about-the-swedish-cancer-society), reference 100351 (to ST).

A conserved feature of the central nervous system (CNS) is the prominent expansion of anterior regions (brain) when compared to posterior (nerve cord). The cellular and regulatory processes driving anterior CNS expansion are not well understood in any bilaterian species. Here, we address this expansion in Drosophila and mouse. We find that when compared to the nerve cord the brain, in both Drosophila and mouse, displays extended progenitor proliferation, more elaborate daughter cell proliferation and more rapid cell cycle speed. These features contribute to anterior CNS expansion in both species. With respect to genetic control, enhanced brain proliferation is severely reduced by ectopic Hox gene expression, by either Hox misexpression or by loss of Polycomb Group (PcG) function. Strikingly, in PcG mutants, early CNS proliferation appears unaffected, whereas subsequently, brain proliferation is severely reduced. Hence, a conserved PcG-Hox program promotes the anterior expansion of the CNS. The profound differences in proliferation and in the underlying genetic mechanisms between brain and nerve cord lend support to the emerging concept of separate evolutionary origins of these two CNS regions.

Synaptic morphology is tightly related to synaptic efficacy, and in many cases morphological synapse defects ultimately lead to synaptic malfunction. The Drosophila larval neuromuscular junction (NMJ), a well-established model for glutamatergic synapses, has been extensively studied for decades. Identification of mutations causing NMJ morphological defects revealed a repertoire of genes that regulate synapse development and function. Many of these were identified in large-scale studies that focused on qualitative approaches to detect morphological abnormalities of the Drosophila NMJ. A drawback of qualitative analyses is that many subtle players contributing to NMJ morphology likely remain unnoticed. Whereas quantitative analyses are required to detect the subtler morphological differences, such analyses are not yet commonly performed because they are laborious. This protocol describes in detail two image analysis algorithms "Drosophila NMJ Morphometrics" and "Drosophila NMJ Bouton Morphometrics", available as Fiji-compatible macros, for quantitative, accurate and objective morphometric analysis of the Drosophila NMJ. This methodology is developed to analyze NMJ terminals immunolabeled with the commonly used markers Dlg-1 and Brp. Additionally, its wider application to other markers such as Hrp, Csp and Syt is presented in this protocol. The macros are able to assess nine morphological NMJ features: NMJ area, NMJ perimeter, number of boutons, NMJ length, NMJ longest branch length, number of islands, number of branches, number of branching points and number of active zones in the NMJ terminal.

Synaptic morphology is tightly related to synaptic efficacy, and in many cases morphological synapse defects ultimately lead to synaptic malfunction. The Drosophila larval neuromuscular junction (NMJ), a well-established model for glutamatergic synapses, has been extensively studied for decades. Identification of mutations causing NMJ morphological defects revealed a repertoire of genes that regulate synapse development and function. Many of these were identified in large-scale studies that focused on qualitative approaches to detect morphological abnormalities of the Drosophila NMJ. A drawback of qualitative analyses is that many subtle players contributing to NMJ morphology likely remain unnoticed. Whereas quantitative analyses are required to detect the subtler morphological differences, such analyses are not yet commonly performed because they are laborious. This protocol describes in detail two image analysis algorithms "Drosophila NMJ Morphometrics" and "Drosophila NMJ Bouton Morphometrics", available as Fiji-compatible macros, for quantitative, accurate and objective morphometric analysis of the Drosophila NMJ. This methodology is developed to analyze NMJ terminals immunolabeled with the commonly used markers Dlg-1 and Brp. Additionally, its wider application to other markers such as Hrp, Csp and Syt is presented in this protocol. The macros are able to assess nine morphological NMJ features: NMJ area, NMJ perimeter, number of boutons, NMJ length, NMJ longest branch length, number of islands, number of branches, number of branching points and number of active zones in the NMJ terminal.

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) substantially challenges TB control, especially in the European Region of the World Health Organization, where the highest prevalence of MDR/XDR cases is reported. The current management of patients with MDR/XDR-TB is extremely complex for medical, social and public health systems. The treatment with currently available anti-TB therapies to achieve relapse-free cure is long and undermined by a high frequency of adverse drug events, suboptimal treatment adherence, high costs and low treatment success rates. Availability of optimal management for patients with MDR/XDR-TB is limited even in the European Region. In the absence of a preventive vaccine, more effective diagnostic tools and novel therapeutic interventions the control of MDR/XDR-TB will be extremely difficult. Despite recent scientific advances in MDR/XDR-TB care, decisions for the management of patients with MDR/XDR-TB and their contacts often rely on expert opinions, rather than on clinical evidence. This document summarises the current knowledge on the prevention, diagnosis and treatment of adults and children with MDR/XDR-TB and their contacts, and provides expert consensus recommendations on questions where scientific evidence is still lacking., TBNET consensus statement on the management of patients with MDR/XDR-TB has been released in the Eur Respir J http://ow.ly/uizRD

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Complexity in the processing of the Amyloid Precursor Protein, which generates a mixture of βamyloid peptides, lies beneath the difficulty in understanding the etiology of Alzheimer's disease. Moreover, whether Aβ peptides have any physiological role in neurons is an unresolved question. By expressing single, defined Aβ peptides in Drosophila, specific effects can be discriminated in vivo. Here, we show that in the adult neuromuscular junction (NMJ), presynaptic expression of Aβ40 hinders the synaptic addition that normally occurs in adults, yielding NMJs with an invariable number of active zones at all ages tested. A similar trend is observed for Aβ42 at young ages, but net synaptic loss occurs at older ages in NMJs expressing this amyloid species. In contrast, Aβ42arc produces net synaptic loss at all ages tested, although age-dependent synaptic variations are maintained. Inhibition of the PI3K synaptogenic pathway may mediate some of these effects, because western analyses show that Aβ peptides block activation of this pathway, and Aβ species-specific synaptotoxic effects persists in NMJs overgrown by over-expression of PI3K. Finally, individual Aβ effects are also observed when toxicity is examined by quantifying neurodegeneration and survival. Our results suggest a physiological effect of Aβ40 in synaptic plasticity, and imply different toxic mechanisms for each peptide species., Centro de Investigación de Enfermedades; Neurológicas - Fundación Reina Sofía Grant PI0006-08 to LT and IC; Ministerio de Ciencia y Tecnología (ES) grant BFU2008-04683-C02-02 to LT; Ministerio de Economía y Competitividad (ES) grant BFU2016-78327-P to LT

A readily evident feature of animal central nervous systems (CNSs), apparent in all vertebrates and many invertebrates alike, is its "wedge-like" appearance, with more cells generated in anterior than posterior regions. This wedge could conceivably be established by an antero-posterior (A-P) gradient in the number of neural progenitor cells, their proliferation behaviors, and/or programmed cell death (PCD). However, the contribution of each of these mechanisms, and the underlying genetic programs, are not well understood. Building upon recent progress in the Drosophila melanogaster (Drosophila) ventral nerve cord (VNC), we address these issues in a comprehensive manner. We find that, although PCD plays a role in controlling cell numbers along the A-P axis, the main driver of the wedge is a gradient of daughter proliferation, with divisions directly generating neurons (type 0) being more prevalent posteriorly and dividing daughters (type I) more prevalent anteriorly. In addition, neural progenitor (NB) cell-cycle exit occurs earlier posteriorly. The gradient of type I0 daughter proliferation switch and NB exit combine to generate radically different average lineage sizes along the A-P axis, differing by more than 3-fold in cell number. We find that the Hox homeotic genes, expressed in overlapping A-P gradients and with a late temporal onset in NBs, trigger the type I0 daughter proliferation switch and NB exit. Given the highly evolutionarily conserved expression of overlapping Hox homeotic genes in the CNS, our results point to a common mechanism for generating the CNS wedge.

The morphology of synapses is of central interest in neuroscience because of the intimate relation with synaptic efficacy. Two decades of gene manipulation studies in different animal models have revealed a repertoire of molecules that contribute to synapse development. However, since such studies often assessed only one, or at best a few, morphological features at a given synapse, it remained unaddressed how different structural aspects relate to one another. Furthermore, such focused and sometimes only qualitative approaches likely left many of the more subtle players unnoticed. Here, we present the image analysis algorithm ‘Drosophila_NMJ_Morphometrics’, available as a Fiji-compatible macro, for quantitative, accurate and objective synapse morphometry of the Drosophila larval neuromuscular junction (NMJ), a well-established glutamatergic model synapse. We developed this methodology for semi-automated multiparametric analyses of NMJ terminals immunolabeled for the commonly used markers Dlg1 and Brp and showed that it also works for Hrp, Csp and Syt. We demonstrate that gender, genetic background and identity of abdominal body segment consistently and significantly contribute to variability in our data, suggesting that controlling for these parameters is important to minimize variability in quantitative analyses. Correlation and principal component analyses (PCA) were performed to investigate which morphometric parameters are inter-dependent and which ones are regulated rather independently. Based on nine acquired parameters, we identified five morphometric groups: NMJ size, geometry, muscle size, number of NMJ islands and number of active zones. Based on our finding that the parameters of the first two principal components hardly correlated with each other, we suggest that different molecular processes underlie these two morphometric groups. Our study sets the stage for systems morphometry approaches at the well-studied Drosophila NMJ., Author Summary Altered synapse function underlies cognitive disorders such as intellectual disability, autism and schizophrenia. The morphology of synapses is crucial for their function but is often described using only a small number of parameters or categories. As a consequence, it is still unknown how different aspects of synapse morphology relate to each other and whether they respond in a coordinated or independent manner. Here, we report a sensitive and multiparametric method for systematic synapse morphometry at the Drosophila Neuromuscular Junction (NMJ), a popular model for mammalian synapse biology. Surveying a large NMJ image repository, we provide insights in the natural variation of NMJ morphology as a result of differences in gender, genetic background and abdominal body segment. We show which synapse parameters correlate and find that parameters fall into five groups. Based on our findings, we propose that two of them, NMJ size and geometry, are controlled by different molecular mechanisms. Our study provides insights into the design principles of a model synapse and tools that can be applied in future studies to identify genes that modulate or co-orchestrate different aspects of synapse morphology.

A recent and controversial hypothesis suggests the presence of an oestrus phase in women as in other mammals. This implies that women at their optimal fertility point of the menstrual cycle exhibit behaviors focused to maximize the genetic quality of their offspring. Several studies support this hypothesis, finding that women in the fertile phase tend to prefer men with traits associated to phenotypic quality, such as greater facial masculinization and symmetry. We experimentally tested some of the observations supporting this hypothesis in a population of 810 young Spanish women. We analyzed whether the preference for masculinized male faces is affected by i) the phase of the menstrual cycle, ii) having a stable partner and iii) the use of birth control pills. We could not reproduce the effect of the first two factors, but we found that women using hormonal contraceptives tend to prefer men with less masculine faces. These results indicate that some of the evidences supporting the oestrus hypothesis in humans must be reviewed, incorporating data from different socio-cultural and ethnic populations. Recientemente se ha postulado una controvertida hipótesis que propone la presencia de un periodo de estro en las mujeres, como ocurre en otros mamíferos. Ello implica que las mujeres en el óptimo de fertilidad del ciclo menstrual presenten comportamientos encaminados a maximizar la calidad genetica de su descendencia. Diversas investigaciones sostienen esta hipótesis, al encontrar que las mujeres en la fase fértil prefieren hombres con rasgos que denotan mayor calidad fenotípica, como un mayor grado de masculinización o una mayor simetría. Nuestro objetivo ha sido testar experimentalmente en una población de 810 jóvenes españolas alguna de estas observaciones. Analizamos si, tal como se recoge en la bibliografía, la preferencia por rostros de hombres masculinizados se ve afectada por i) la etapa del ciclo menstrual, ii) el tener pareja estable y iii) el empleo anticonceptivos hormonales. No hemos podido reproducir el efecto de los dos primeros factores, pero si encontramos que las mujeres que emplean anticonceptivos hormonales prefirieron rostros de hombre menos masculinos. Estos resultados no refutan la hipótesis del estro en humanos, pero nos indican que algunas de las pruebas que la sustentan han de ser reconsideradas, incorporando datos de poblaciones étnica y socioculturalmente diferentes.

A recent and controversial hypothesis suggests the presence of an oestrus phase in women as in other mammals. This implies that women at their optimal fertility point of the menstrual cycle exhibit behaviors focused to maximize the genetic quality of their offspring. Several studies support this hypothesis, finding that women in the fertile phase tend to prefer men with traits associated to phenotypic quality, such as greater facial masculinization and symmetry. We experimentally tested some of the observations supporting this hypothesis in a population of 810 young Spanish women. We analyzed whether the preference for masculinized male faces is affected by i) the phase of the menstrual cycle, ii) having a stable partner and iii) the use of birth control pills. We could not reproduce the effect of the first two factors, but we found that women using hormonal contraceptives tend to prefer men with less masculine faces. These results indicate that some of the evidences supporting the oestrus hypothesis in humans must be reviewed, incorporating data from different socio-cultural and ethnic populations.

It is becoming increasingly clear that the activation of specific terminal differentiation genes during neural development is critically dependent upon the establishment of unique combinatorial transcription factor codes within distinct neural cell subtypes. However, it is still unclear to which extent these codes are shared by lineage-unrelated neurons expressing the same terminal differentiation genes. Additionally, it is not known if the activation of a specific terminal differentiation gene is restricted to cells born at a particular developmental time point. Here, we utilize the terminal differentiation gene FMRFa which is expressed by the Ap4 and SE2 neurons in the Drosophila ventral nerve cord, to explore these issues in depth. We find that the Ap4 and SE2 neurons are generated by different neural progenitors and use different combinatorial codes to activate FMRFa expression. Additionally, we find that the Ap4 and SE2 neurons are generated in different temporal gene expression windows. Extending the investigation to include a second Drosophila terminal differentiation gene, Leucokinin, we find similar results, suggesting that neurons generated by different progenitors might commonly use different transcription factor codes to activate the same terminal differentiation gene. Furthermore, these results imply that the activation of a particular terminal differentiation gene in temporally unrestricted., This work was supported by a grant from the Spanish Ministerio de Ciencia e Innovación (BFU-2008- 04683-C02-02 to L.T.).

Chronic stress by immobilization during pregnancy may cause alterations in mechanisms maintaining homeostasis in the adrenal gland. The objective of this study was to quantify cellular proliferation index in the adrenal cortex during pregnancy second half and assess the effects of chronic stress on it. Adrenal cortex proliferation index in stressed rats showed a significant decrease at 12 and 17 days of gestation, while at day 21 it did not show differences with the control treatments. Moreover, proliferation index of reticular zones in control and experimental rats, exhibited a significant reduction in comparison to glomerular and fascicular zones of adrenal cortex during the three gestation days studied. In conclusion, chronic stress by immobilization produces a decrease in cellular proliferation index at 12 and 17 gestation days, which may be related to changes in plasmatic concentrations of corticosterone and prolactin and, to the reduction of specific growth factors. Furthermore, the observed proliferation diminishment in reticular zone regarding the other cortical zones would be consistent with the migration theory of adrenal cells, El estrés crónico por inmovilización durante la gestación puede provocar alteraciones de los mecanismos que mantienen la homeostasis en la glándula adrenal. El objetivo de este trabajo fue cuantificar el índice de proliferación en la corteza adrenal durante la segunda mitad de la gestación y comprobar los efectos que produce el estrés crónico sobre el mismo. El índice de proliferación en la corteza adrenal de ratas estresadas presentó una disminución significativa a los 12 y 17 días de gestación, mientras que en el día 21 no presentó modificaciones con respecto a sus controles. Por otro lado, el índice de proliferación de la zona reticular en ratas controles y experimentales, presentó una disminución significativa con respecto a las zonas glomerular y fascicular de la corteza adrenal en los tres días de la gestación estudiados. Se puede concluir que el estrés crónico por inmovilización produce disminución del índice de proliferación celular a los 12 y 17 días de la gestación que podría estar en relación con las variaciones de las concentraciones plasmáticas de corticosterona, prolactina, y con la disminución de factores de crecimiento específicos. Asimismo, la disminución de la proliferación en la zona reticular en relación con las otras zonas corticales estaría en concordancia con la teoría de la migración celular adrenal