1,747 research outputs found
A rare constellation of multiple upper limb anomalies
We describe an unusual combination of unilateral upper limb variations, including
an axillary arch, absence of a “typical” musculocutaneous nerve, direct
lateral cord innervation of the muscles usually supplied by the musculocutaneous
nerve, variant superficial brachial artery, a high anomalous origin of the
common interosseous artery and a superficial ulnar artery noted during routine
cadaver dissection. The embryological basis, recent molecular insights concerning
such a constellation of anomalies and its clinical relevance are discussed
Association of occupational exposure on semen density in male industrial workers undergoing infertility treatment at tertiary care hospital
Background: Working with particular substances or under certain working situations may cause some workers to experience abnormalities in their sexual or reproductive health. Occupational exposures can lead to infertility, but the workers may not be aware of such problems. The purpose of the study was to determine the association between male infertility and occupation of industrial workers in organized sector.Methods: Prospective case-controlled study that included 136 industrial workers working in organized sector and attending infertility clinic for treatment. This study included male partners aged between 21-46 years with primary or secondary infertility and undertaking same occupation for at least last three months. Complete infertility workup of all male partners attending infertility clinic was done that included detailed history and information related to occupation. Routine semen parameters were evaluated according to the 2010 World Health Organization (WHO) criteria.Results: In the present study, significant semen abnormalities were observed in male partners with age more than 31 years and undertaking arduous jobs for more than 5 years (p <0.05) in study group (n=136) as compared to control group (n=62). The abnormal semen count were observed in 114 (83.2%) workers in the study group that included 43 (31.6%) with total sperm concentration (TSC) less than 10 million/ml and azoospermia in 44 (32.3%). Reduced motility (asthenozoo-spermia) was observed in majority 125 (91.9%) of male partners. The findings were significant (p <0.05) as compared to control group.Conclusions: Preventive measures in the workplace need to be established to reduce the effect of occupational hazards and its influence in the semen parameters ultimately leading to infertility
Identification of Sesamin from Sesamum indicum as a Potent Antifungal Agent Using an Integrated in Silico and Biological Screening Platform
Due to the limited availability of antifungal drugs, their relevant side effects and considering the insurgence of drug-resistant strains, novel antifungal agents are urgently needed. To identify such agents, we have developed an integrated computational and biological screening platform. We have considered a promising drug target in antifungal drug discovery (exo-1,3-β-glucanase) and a phytochemical library composed of bioactive natural products was used. These products were computationally screened against the selected target using molecular docking and molecular dynamics techniques along with the evaluation of drug-like profile. We selected sesamin as the most promising phytochemical endowed with a potential antifungal profile and satisfactory drug-like properties. Sesamin was submitted to a preliminary biological evaluation to test its capability to inhibit the growth of several Candida species by calculating the MIC/MFC and conducting synergistic experiments with the marketed drug fluconazole. Following the screening protocol, we identified sesamin as a potential exo-1,3-β-glucanase inhibitor, with relevant potency in inhibiting the growth of Candida species in a dose-dependent manner (MIC and MFC of 16 and 32 μg/mL, respectively). Furthermore, the combination of sesamin with fluconazole highlighted relevant synergistic effects. The described screening protocol revealed the natural product sesamin as a potential novel antifungal agent, showing an interesting predicted pharmacological profile, paving the way to the development of innovative therapeutics against fungal infections. Notably, our screening protocol can be helpful in antifungal drug discovery
Toric Calabi-Yau supermanifolds and mirror symmetry
We study mirror symmetry of supermanifolds constructed as fermionic
extensions of compact toric varieties. We mainly discuss the case where the
linear sigma A-model contains as many fermionic fields as there are U(1)
factors in the gauge group. In the mirror super-Landau-Ginzburg B-model, focus
is on the bosonic structure obtained after integrating out all the fermions.
Our key observation is that there is a relation between the super-Calabi-Yau
conditions of the A-model and quasi-homogeneity of the B-model, and that the
degree of the associated superpotential in the B-model is given in terms of the
determinant of the fermion charge matrix of the A-model.Comment: 20 pages, v2: references adde
Numerical computation of electric field and potential along silicone rubber insulators under contaminated and dry band conditions
Progress in the Early Solar System Chronology: A Sketch of an Ever-Changing Landscape
The years since the Workshop on the Chronology of Meteorites and the Early Solar System, are marked with ongoing progress in cosmochronology. Rapid improvements in techniques, discovery of new meteorites unlike any previously known, and findings that what was deemed well established constants are actually variables, will be reflected in an updated review of the solar system chronology we are currently preparing. Along with updating the database of meteorite ages, it will involve development of a set of criteria for evaluation of accuracy and consistency of isotopic dates across the entire range of meteorite classes and isotope chronometer systems. Here we present some ideas on what we think is important in meteorite chronology, and invite the cosmochemistry community to discuss them
MortaparibPlus- A Novel Anticancer Small Molecule Abrogating Mortalin-p53 Interaction in Cancer Cells
Background. The cessation of tumor cell growth through cell cycle arrest and apoptosis is determined by p53, a tumor suppressor protein. However, the interaction between mortalin-p53 within cytoplasm/nucleus leads to the inactivation of p53 transcriptional activation function. The disruption of mortalin-p53 complex has been suggested as an approach for developing a potential anticancer drug.
Methods. A screening of a high-content chemical library was performed to determine a molecule with mortalin-p53-interaction disrupting characteristics. After four-rounds of visual assays, we discovered a triazole derivative (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole, named MortaparibPlus) with a potential ability of disrupting mortalin-p53-complex. In this study, we recruited two types of cells (different p53 status and point mutation), Colorectal Cancer Cells [HCT116 (p53WT) and DLD-1 (p53 (p53S241F)] and Luminal A Breast Cancer [MCF-7 (p53WT) and T47D (p53L194F)]. We further validated the activity of MortaparibPlus by bioinformatics/experimental analyses.
Results. Through bioinformatics analysis, we discovered that MortaparibPlus has potential to block the binding site of mortalin on p53, thus, preventing the formation of mortalin-p53 complex. Immunoprecipitation analyses showed that MortaparibPlus abrogated the mortalin-p53 complex formation and caused growth arrest/apoptosis (via activation of p21WAF1, BAX, and PUMA) in HCT116, DLD-1, and MCF-7 cells. Furthermore, MortaparibPlus posed a cytotoxic effect to cancer cells through various mechanisms (inhibition of PARP1, up-regulation of p73 proteins, downregulation of mortalin and CARF proteins). In contrast, we found that, despite the hyperactivation of PARP1 (PAR accumulation and loss of ATP) as an alternative tumor suppression mechanism, MortaparibPlus-treated T47D cells exhibited signs of neither complete apoptosis nor PAR-Thanatos. Such response was associated with the failure of MortaparibPlus to inhibit the formation of AIF-mortalin complexes.
Conclusions. MortaparibPlus is proposed as a potential multimodal small molecule for cancer treatment that requires further extensive laboratory and clinical studies
Intergenerational Effect of Maternal Exposure to Childhood Maltreatment on Newborn Brain Anatomy
Background Childhood maltreatment (CM) confers deleterious long-term consequences, and growing evidence suggests some of these effects may be transmitted across generations. We examined the intergenerational effect of maternal CM exposure on child brain structure and also addressed the hypothesis that this effect may start during the child's intrauterine period of life. Methods A prospective longitudinal study was conducted in a clinical convenience sample of 80 mother-child dyads. Maternal CM exposure was assessed using the Childhood Trauma Questionnaire. Structural magnetic resonance imaging was employed to characterize newborn global and regional brain (tissue) volumes near the time of birth. Results CM exposure was reported by 35% of the women. Maternal CM exposure was associated with lower child intracranial volume (F1,70 = 6.84, p =.011), which was primarily due to a global difference in cortical gray matter (F1,70 = 9.10, p =.004). The effect was independent of potential confounding variables, including maternal socioeconomic status, obstetric complications, obesity, recent interpersonal violence, pre- and early postpartum stress, gestational age at birth, infant sex, and postnatal age at magnetic resonance imaging scan. The observed group difference between offspring of CM-exposed mothers versus nonexposed mothers was 6%. Conclusions These findings represent the first report to date associating maternal CM exposure with variation in newborn brain structure. These observations support our hypothesis of intergenerational transmission of the effects of maternal CM exposure on child brain development and suggest this effect may originate during the child's intrauterine period of life, which may have downstream neurodevelopmental consequences
Using VSWIR Microimaging Spectroscopy to Explore the Mineralogical Diversity of HED Meteorites
We use VSWIR microimaging spectroscopy to survey the spectral diversity of HED meteorites at 80-μm/pixel spatial scale. Our goal in this work is both to explore the emerging capabilities of microimaging VSWIR spectroscopy and to contribute to understanding the petrologic diversity of the HED suite and the evolution of Vesta. Using a combination of manual and automated hyperspectral classification techniques, we identify four major classes of materials based on VSWIR absorptions that include pyroxene, olivine, Fe-bearing feldspars, and glass-bearing/featureless materials. Results show microimaging spectroscopy is an effective method for rapidly and non-destructively characterizing small compositional variations of meteorite samples and for locating rare phases for possible follow-up investigation. Future work will include incorporating SEM/EDS results to quantify sources of spectral variability and placing observations within a broader geologic framework of the differentiation and evolution of Vesta
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