Male pygmy hippopotamus influence offspring sex ratio

Pre-determining fetal sex is against the random and equal opportunity that both conceptus sexes have by nature. Yet, under a wide variety of circumstances, populations shift their birth sex ratio from the expected unity. Here we show, using fluorescence in situ hybridization, that in a population of pygmy hippopotamus (Choeropsis liberiensis) with 42.5% male offspring, males bias the ratio of X- and Y-chromosome-bearing spermatozoa in their ejaculates, resulting in a 0.4337±0.0094 (mean±s.d.) proportion of Y-chromosome-bearing spermatozoa. Three alternative hypotheses for the shifted population sex ratio were compared: female counteract male, female indifferent, or male and female in agreement. We conclude that there appears little or no antagonistic sexual conflict, unexpected by prevailing theories. Our results indicate that males possess a mechanism to adjust the ratio of X- and Y-chromosome-bearing spermatozoa in the ejaculate, thereby substantially expanding currently known male options in sexual conflict

Anthropic resource exploitation and use of the territory at the onset of social complexity in the Neolithic-Chalcolithic Western Pyrenees: a multi-isotope approach

Carbon (δ13C) and nitrogen (δ15N) stable isotope analyses from bone collagen provide information about the dietary protein input, while strontium isotopes (87Sr/86Sr) from tooth enamel give us data about provenance and potential territorial mobility of past populations. To date, isotopic results on the prehistory of the Western Pyrenees are scarce. In this article, we report human and faunal values of the mentioned isotopes from the Early-Middle Neolithic site of Fuente Hoz (Anuntzeta) and the Late Neolithic/Early Chalcolithic site of Kurtzebide (Letona, Zigoitia). The main objectives of this work are to analyze the dietary and territorial mobility patterns of these populations. Furthermore, as an additional aim, we will try to discuss social ranking based on the isotope data and existing literature on this topic in the region of study. Our results show that, based on the bioavailable Sr values, both purported local and non-local humans were buried together at the sites. Additionally, they suggest similar resource consumption based on C3 terrestrial resources (i.e. ovicaprids, bovids, and suids) as the main part of the protein input. Overall, this study sheds light on how individuals from different backgrounds were still buried together and shared the same dietary lifestyle at a time in the Prehistory of Iberia when social complexities started to appear

Cheek Tooth Morphology and Ancient Mitochondrial DNA of Late Pleistocene Horses from the Western Interior of North America: Implications for the Taxonomy of North American Late Pleistocene Equus

Horses were a dominant component of North American Pleistocene land mammal communities and their remains are well represented in the fossil record. Despite the abundant material available for study, there is still considerable disagreement over the number of species of Equus that inhabited the different regions of the continent and on their taxonomic nomenclature. In this study, we investigated cheek tooth morphology and ancient mtDNA of late Pleistocene Equus specimens from the Western Interior of North America, with the objective of clarifying the species that lived in this region prior to the end-Pleistocene extinction. Based on the morphological and molecular data analyzed, a caballine (Equus ferus) and a non-caballine (E. conversidens) species were identified from different localities across most of the Western Interior. A second non-caballine species (E. cedralensis) was recognized from southern localities based exclusively on the morphological analyses of the cheek teeth. Notably the separation into caballine and non-caballine species was observed in the Bayesian phylogenetic analysis of ancient mtDNA as well as in the geometric morphometric analyses of the upper and lower premolars. Teeth morphologically identified as E. conversidens that yielded ancient mtDNA fall within the New World stilt-legged clade recognized in previous studies and this is the name we apply to this group. Geographic variation in morphology in the caballine species is indicated by statistically different occlusal enamel patterns in the specimens from Bluefish Caves, Yukon Territory, relative to the specimens from the other geographic regions. Whether this represents ecomorphological variation and/or a certain degree of geographic and genetic isolation of these Arctic populations requires further study

Clinical practice: Coeliac disease

Coeliac disease (CD) is an immune-mediated systemic condition elicited by gluten and related prolamines in genetically predisposed individuals and characterised by gluten-induced symptoms and signs, specific antibodies, a specific human leukocyte antigen (HLA) type and enteropathy. The risk of coeliac disease is increased in first-degree relatives, certain syndromes including Down syndrome and autoimmune disorders. It is thought to occur in 1 in 100–200 individuals, but still only one in four cases is diagnosed. Small-bowel biopsy is no longer deemed necessary in a subgroup of patients, i.e. when all of the following are present: typical symptoms or signs, high titres of and transglutaminase antibodies, endomysial antibodies, and HLA-type DQ2 or DQ8. In all other cases, small-bowel biopsy remains mandatory for a correct diagnosis. Therapy consists of a strictly gluten-free diet. This should result in complete disappearance of symptoms and of serological markers. Adequate follow-up is considered essential. Conclusion: Although small-bowel biopsy may be omitted in a minority of patients, small-bowel biopsy is essential for a correct diagnosis of CD in all other cases. Diagnostic work-up should be completed before treatment with gluten-free diet instituted

Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine

BACKGROUND: The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals. RESULTS: Viral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ΔRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine γ-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ΔRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ΔRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors. CONCLUSIONS: We propose that immature HIV-1 virions generated from NL4-3/ΔRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles.This study was supported by grants FIS PI050265, FIS PI040503, FIS PI070291, FIS Intrasalud 080752, FIS PS09/01297, FIS PI10/02984, SAF2006-26667-E, FIT 09-010-205-9, FIPSE 36780/08, Fundación Mútua Madrileña, TRA-094, EC10-153, ISCIII-RETIC RD06/0006, HIVACAT–HIV Development Program in Catalonia, FIPSE 36630/07, UE Program Health 2009 CHAARM. Spanish Health Institute Carlos III (ISCIII) and the Health Department of the Catalan Government (Generalitat de Catalunya). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Super-silent FRET Sensor Enables Live Cell Imaging and Flow Cytometric Stratification of Intracellular Serine Protease Activity in Neutrophils

Abstract Serine proteases are released by neutrophils to act primarily as antimicrobial proteins but excessive and unbalanced serine protease activity results in serious host tissue damage. Here the synthesis of a novel chemical sensor based on a multi-branched fluorescence quencher is reported. It is super-silent, exhibiting no fluorescence until de-quenched by the exemplar serine protease human neutrophil elastase, rapidly enters human neutrophils, and is inhibited by serine protease inhibitors. This sensor allows live imaging of intracellular serine protease activity within human neutrophils and demonstrates that the unique combination of a multivalent scaffold combined with a FRET peptide represents a novel and efficient strategy to generate super-silent sensors that permit the visualisation of intracellular proteases and may enable point of care whole blood profiling of neutrophils

Current Data on and Clinical Insights into the Treatment of First Episode Nonaffective Psychosis: A Comprehensive Review

Implementing the most suitable treatment strategies and making appropriate clinical decisions about individuals with a first episode of psychosis (FEP) is a complex and crucial task, with relevant impact in illness outcome. Treatment approaches in the early stages should go beyond choosing the right antipsychotic drug and should also address tractable factors influencing the risk of relapse. Effectiveness and likely metabolic and endocrine disturbances differ among second-generation antipsychotics (SGAs) and should guide the choice of the first-line treatment. Clinicians should be aware of the high risk of cardiovascular morbidity and mortality in schizophrenia patients, and therefore monitoring weight and metabolic changes across time is mandatory. Behavioral and counseling interventions might be partly effective in reducing weight gain and metabolic disturbances. Ziprasidone and aripiprazole have been described to be least commonly associated with weight gain or metabolic changes. In addition, some of the SGAs (risperidone, amisulpride, and paliperidone) have been associated with a significant increase of plasma prolactin levels. Overall, in cases of FEP, there should be a clear recommendation of using lower doses of the antipsychotic medication. If no or minimal clinical improvement is found after 2 weeks of treatment, such patients may benefit from a change or augmentation of treatment. Clinicians should provide accurate information to patients and relatives about the high risk of relapse if antipsychotics are discontinued, even if patients have been symptom free and functionally recovered on antipsychotic treatment for a lengthy period of time.This review was carried out at the Hospital Marque´s de Valdecilla, University of Cantabria, Santander, Spain, with the following Grant support: Instituto de Salud Carlos III PI020499, PI050427, PI060507, Plan Nacional de Drugs Research Grant 2005-Orden sco/3246/2004, SENY Fundacio´ Research Grant CI 2005-0308007, Fundacio´n Marque´s de Valdecilla API07/011 and CIBERSAM

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field