In the mammalian model of sex determination, embryos are considered to be sexually indifferent until the transient action of a sex-determining gene initiates gonadal differentiation. Although this ...model is thought to apply to all vertebrates, this has yet to be established. Here we have examined three lateral gynandromorph chickens (a rare, naturally occurring phenomenon in which one side of the animal appears male and the other female) to investigate the sex-determining mechanism in birds. These studies demonstrated that gynandromorph birds are genuine male:female chimaeras, and indicated that male and female avian somatic cells may have an inherent sex identity. To test this hypothesis, we transplanted presumptive mesoderm between embryos of reciprocal sexes to generate embryos containing male:female chimaeric gonads. In contrast to the outcome for mammalian mixed-sex chimaeras, in chicken mixed-sex chimaeras the donor cells were excluded from the functional structures of the host gonad. In an example where female tissue was transplanted into a male host, donor cells contributing to the developing testis retained a female identity and expressed a marker of female function. Our study demonstrates that avian somatic cells possess an inherent sex identity and that, in birds, sexual differentiation is substantively cell autonomous.
Wind blowing over sand on Earth produces decimeter-wavelength ripples and hundred-meter— to kilometer-wavelength dunes: bedforms of two distinct size modes. Observations from the Mars Science ...Laboratory Curiosity rover and the Mars Reconnaissance Orbiter reveal that Mars hosts a third stable wind-driven bedform, with meter-scale wavelengths. These bedforms are spatially uniform in size and typically have asymmetric profiles with angle-of-repose lee slopes and sinuous crest lines, making them unlike terrestrial wind ripples. Rather, these structures resemble fluid-drag ripples, which on Earth include water-worked current ripples, but on Mars instead form by wind because of the higher kinematic viscosity of the low-density atmosphere. A reevaluation of the wind-deposited strata in the Burns formation (about 3.7 billion years old or younger) identifies potential wind-drag ripple stratification formed under a thin atmosphere.
Enteric viruses like norovirus, rotavirus and astrovirus have long been accepted as spreading in the population through fecal-oral transmission: viruses are shed into feces from one host and enter ...the oral cavity of another, bypassing salivary glands (SGs) and reaching the intestines to replicate, be shed in feces and repeat the transmission cycle
. Yet there are viruses (for example, rabies) that infect the SGs
, making the oral cavity one site of replication and saliva one conduit of transmission. Here we report that enteric viruses productively and persistently infect SGs, reaching titres comparable to those in the intestines. We demonstrate that enteric viruses get released into the saliva, identifying a second route of viral transmission. This is particularly significant for infected infants, whose saliva directly transmits enteric viruses to their mothers' mammary glands through backflow during suckling. This sidesteps the conventional gut-mammary axis route
and leads to a rapid surge in maternal milk secretory IgA antibodies
. Lastly, we show that SG-derived spheroids
and cell lines
can replicate and propagate enteric viruses, generating a scalable and manageable system of production. Collectively, our research uncovers a new transmission route for enteric viruses with implications for therapeutics, diagnostics and importantly sanitation measures to prevent spread through saliva.
Most oral cancers are oral squamous cell carcinomas (OSCC) that arise from the epithelial lining of the oral mucosa. Given that the oral cavity is easily accessible, the disease lends itself to early ...detection; however, most oral cancers are diagnosed at a late stage, and approximately half of oral cancer sufferers do not survive beyond five years, post-diagnosis. The low survival rate has been attributed to late detection, but there is no accepted, reliable and convenient method for the detection of oral cancer and oral pre-cancer. Dielectrophoresis (DEP) is a label-free technique which can be used to obtain multi-parametric measurements of cell electrical properties. Parameters such as cytoplasmic conductivity and effective membrane capacitance (
C
Eff
) can be non-invasively determined by the technique. In this study, a novel lab-on-a-chip device was used to determine the cytoplasmic conductivity and
C
Eff
of primary normal oral keratinocytes, and pre-cancerous and cancerous oral keratinocyte cell lines. Our results show that the electrical properties of normal, pre-cancerous and cancerous oral keratinocytes are distinct. Furthermore, increasing
C
Eff
and decreasing cytoplasmic conductivity correlate with disease progression which could prove significant for diagnostic and prognostic applications. DEP has the potential to be used as a non-invasive technique to detect oral cancer and oral pre-cancer. Clinical investigation is needed to establish the reliability and temporal relationship of the correlation between oncologic disease progression and the electrical parameters identified in this study. To use this technique as an OSCC detection tool in a clinical setting, further characterisation and refinement is warranted.
A revision of the 2008 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken in order to incorporate new evidence ...and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in September 2012. Key areas in treating depression were reviewed and the strength of evidence and clinical implications were considered. The guidelines were then revised after extensive feedback from participants and interested parties. A literature review is provided which identifies the quality of evidence upon which the recommendations are made. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse and stopping treatment. Significant changes since the last guidelines were published in 2008 include the availability of new antidepressant treatment options, improved evidence supporting certain augmentation strategies (drug and non-drug), management of potential long-term side effects, updated guidance for prescribing in elderly and adolescent populations and updated guidance for optimal prescribing. Suggestions for future research priorities are also made.
Logistic regression studies which assess landslide susceptibility are widely available in the literature. However, a global review of these studies to synthesise and compare the results does not ...exist. There are currently no guidelines for the selection of covariates to be used in logistic regression analysis, and as such, the covariates selected vary widely between studies. An inventory of significant covariates associated with landsliding produced from the full set of such studies globally would be a useful aid to the selection of covariates in future logistic regression studies. Thus, studies using logistic regression for landslide susceptibility estimation published in the literature were collated, and a database was created of the significant factors affecting the generation of landslides. The database records the paper the data were taken from, the year of publication, the approximate longitude and latitude of the study area, the trigger method (where appropriate) and the most dominant type of landslides occurring in the study area. The significant and non-significant (at the 95 % confidence level) covariates were recorded, as well as their coefficient, statistical significance and unit of measurement. The most common statistically significant covariate used in landslide logistic regression was slope, followed by aspect. The significant covariates related to landsliding varied for earthquake-induced landslides compared to rainfall-induced landslides, and between landslide type. More importantly, the full range of covariates used was identified along with their frequencies of inclusion. The analysis showed that there needs to be more clarity and consistency in the methodology for selecting covariates for logistic regression analysis and in the metrics included when presenting the results. Several recommendations for future studies were given.
Fractures of the hip are common, often occurring in frail elderly patients, but also in younger fit healthy patients following trauma. They have a significant associated mortality and major social ...and financial implications to patients and health care providers. Many guidelines are available for the management of these patients, mostly recommending early surgery for the best outcomes. As a result, healthcare authorities now put pressure on surgical teams to 'fast track' patients with a fracture of the hip, often misquoting the available literature, which in itself can be confusing and even conflicting. This paper has been written following an extensive review of the available literature. An attempt is made to clarify what is meant by early surgery (expeditious versus emergency), and we conclude with a personal view for the practical management of these patients of variable age, fitness and type of surgery performed within services that are often under considerable pressure of finance and available operating theatres and qualified staff. Cite this article: Bone Joint J 2016;98-B:1573-81.
By 2010 there had been 14 published trials of surgery for intracerebral hemorrhage reported in systematic reviews or to the authors, but the role and timing of operative intervention remain ...controversial and the practice continues to be haphazard. This study attempted to obtain individual patient data from each of the 13 studies published since 1985 to better define groups of patients that might benefit from surgery.
Authors of identified published articles were approached by mail, e-mail, and at conferences and invited to take part in the study. Data were obtained from 8 studies (2186 cases). Individual patient data included patient's age, Glasgow Coma Score at presentation, volume and site of hematoma, presence of intraventricular hemorrhage, method of evacuation, time to randomization, and outcome.
Meta-analysis indicated that there was improved outcome with surgery if randomization was corrected undertaken within 8 hours of ictus (P=0.003), or the volume of the hematoma was 20 to 50 mL (P=0.004), or the Glasgow Coma Score was between 9 and 12 (P=0.0009), or the patient was aged between 50 and 69 years (P=0.01). In addition, there was some evidence that more superficial hematomas with no intraventricular hemorrhage might also benefit (P=0.09).
There is evidence that surgery is of benefit if undertaken early before the patient deteriorates. This work identifies areas for further research. Ongoing studies in subgroups of patients such as the Surgical Trial in Lobar Intracerebral Hemorrhage (STICH II) will confirm whether these interpretations can be replicated.
Skeletal muscle (SkM) regenerates following injury, replacing damaged tissue with high fidelity. However, in serious injuries, non-regenerative defects leave patients with loss of function, increased ...re-injury risk and often chronic pain. Progress in treating these non-regenerative defects has been slow, with advances only occurring where a comprehensive understanding of regeneration has been gained. Tissue engineering has allowed the development of bioengineered models of SkM which regenerate following injury to support research in regenerative physiology. To date, however, no studies have utilised human myogenic precursor cells (hMPCs) to closely mimic functional human regenerative physiology.
Here we address some of the difficulties associated with cell number and hMPC mitogenicity using magnetic association cell sorting (MACS), for the marker CD56, and media supplementation with fibroblast growth factor 2 (FGF-2) and B-27 supplement. Cell sorting allowed extended expansion of myogenic cells and supplementation was shown to improve myogenesis within engineered tissues and force generation at maturity. In addition, these engineered human SkM regenerated following barium chloride (BaCl
) injury. Following injury, reductions in function (87.5%) and myotube number (33.3%) were observed, followed by a proliferative phase with increased MyoD+ cells and a subsequent recovery of function and myotube number. An expansion of the Pax7+ cell population was observed across recovery suggesting an ability to generate Pax7+ cells within the tissue, similar to the self-renewal of satellite cells seen in vivo.
This work outlines an engineered human SkM capable of functional regeneration following injury, built upon an open source system adding to the pre-clinical testing toolbox to improve the understanding of basic regenerative physiology.
We develop and validate a new algorithm called
primary track recovery
(ptr) that effectively deconvolves known physics and detector effects from nuclear recoil tracks in gas time projection chambers ...(TPCs) with high-resolution readout. This gives access to the primary track charge, length, and vector direction (helping to resolve the “head-tail” ambiguity). Additionally, ptr provides a measurement of the transverse and longitudinal diffusion widths, which can be used to determine the absolute position of tracks in the drift direction for detector fiducialization. Using simulated helium recoils in an atmospheric pressure TPC with a 70:30 mixture of
He:CO
2
we compare the performance of ptr to traditional methods for all key track variables. We find that the algorithm reduces reconstruction errors, including those caused by charge integration, for tracks with mean length-to-width ratios 1.4 and above, corresponding to recoil energies of 20 keV and above in the studied TPCs. We show that ptr improves on existing methods for head-tail disambiguation, particularly for highly inclined tracks, and improves the determination of the absolute position of recoils on the drift axis via transverse diffusion. We find that ptr can partially recover charge structure integrated out by the detector in the
z
direction, but that its determination of energy and length have worse resolution compared to existing methods. We use experimental data to qualitatively verify these findings and discuss implications for future directional detectors at the low-energy frontier.
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