Miracle-dz/UniFAR-FTUs huggingface dataset:
An intracellular analysis of geniculo‐cortical connectivity in area 17 of the cat.

The latencies of excitatory and inhibitory post‐synaptic potentials (e.p.s.p.s and i.p.s.p.s) evoked by electrical stimulation of afferents from the lateral geniculate nucleus were recorded in neurones of area 17 of the cat visual cortex. After application of an extrapolation procedure to compensate for the conduction time of the afferent axons, a histogram of latencies formed three distinct peaks. Potentials in each of these were interpreted as being mediated by mono‐, di‐ and trisynaptic pathways. Characteristic laminar differences in the extracellular field potentials evoked from the lateral geniculate nucleus (l.g.n.) and in the antidromic activation of neurones from the l.g. n. and superior colliculus were used to determine the laminar position of recorded neurones. It was found that within a given layer, all cells maintained similar connexions with relay cells in the l.g. n. Cells in layers 3, 4, upper 5 and 6 were monosynaptically excited by geniculate afferents, while cells in layers 2 and lower 5 received only indirect excitation via other cortical neurones. Layer 3 cells were unique in receiving a prominent disynaptic e.p.s.p. in addition to the direct excitation from the l.g. n. Late, trisynaptic e.p.s.p. components were seen in many layer 5 and 6 cells. The orderly laminar arrangement of the connexions had the consequence that identified cortico‐geniculate neurones were monosynaptically excited and cortico‐collicular neurones di‐ and trisynaptically excited by geniculate afferents. Cortico‐cortical neurones in layers 2 and 3 received di‐ or mono‐ plus disynaptic excitation, depending on laminar position. Post‐synaptic inhibitory potentials were evoked in all impaled cells, following stimulation of the geniculo‐cortical pathway. Except for a few layer 2 cells, this inhibition was mediated through disynaptic pathways of the feed‐forward type. There was a good positive correlation between conduction times for monosynaptic e.p.s.p.s and disynaptic i.p.s.p.s in the same cells, suggesting that cortical neurones receive excitation and inhibition from the same type of geniculate afferents. The stimulating electrodes activated not only geniculo‐cortical afferents, but antidromically activated cortical efferent neurones from their extracortical axons. These neurones possess intracortical collaterals, and care must be taken to distinguish the resulting potentials from those mediated by orthodromic activation of geniculate afferents. In doing so, evidence was obtained for excitatory connexions from layers 2 and 3 to layer 5, from layer 5 to layer 6, and from layer 6 to layer 4. Typical recurrent inhibition was not observed. (ABSTRACT TRUNCATED AT 400 WORDS)
Gynecologic Cancer InterGroup (GCIG) Consensus Review for Clear Cell Carcinoma of the Ovary

Abstract Clear cell carcinoma of the ovary (CCC) is a histologic subtype of epithelial ovarian cancer with a distinct clinical behavior. There are marked geographic differences in the prevalence of CCC. The CCC is more likely to be detected at an early stage than high-grade serous cancers, and when confined within the ovary, the prognosis is good. However, advanced disease is associated with a very poor prognosis and resistance to standard treatment. Cytoreductive surgery should be performed for patients with stage II, III, or IV disease. An international phase III study to compare irinotecan/cisplatin and paclitaxel/carboplatin as adjuvant chemotherapy for stage IIV CCC has completed enrollment (GCIG/JGOG3017). Considering the frequent PIK3CA mutation in CCC, dual inhibitors targeting PI3K, AKT in the mTOR pathway, are promising. Performing these trials and generating the evidence will require considerable international collaboration.
A comparison between the two methods of magnesium sulfate administration for duration of 12 versus 24 h after delivery in patients with severe preeclampsia

Abstract Objectives: To compare between the two methods of magnesium sulfate administration for duration of 12 versus 24 h after delivery in patients with severe preeclampsia. Method: The study was performed as a randomized clinical trial on 182 cases of severe preeclampsia. In one group, Mg sulfate (MgSO4) was prescribed for 12 h after delivery and, in the other group, it was prescribed for 24 h after delivery. Both groups were compared for occurrence of convulsion and other adverse effects. Results: The women of the two groups did not have significant difference according to age, BMI, parity and gravidity, gestational age at the time of delivery. Also, systolic blood pressure, diastolic blood pressure, antihypertensive use, previous diabetes and renal disorders, gestational diabetes, and proteinuria were similar in both groups before treatment. One woman had convulsion in the 12-h group and MgSO4 was continued for 24 h in this case. Blood pressure, urine volume, and laboratory indexes did not show significant differences between the two groups before and after treatment. Also, adverse effects were similar in both groups. Pain of the injection site was less in the 12-h group (p = 0.048). Conclusion: Administration of MgSO4 for a duration of 12 h after delivery should be considered somehow as effective as 24 h prescription for preventing convulsion after delivery.
HLA associations in schizophrenia: Are we re‐discovering the wheel?

Associations between human leukocyte antigen (HLA) polymorphisms on chromosome 6p and schizophrenia (SZ) risk have been evaluated for over five decades. Numerous case–control studies from the candidate gene era analyzed moderately sized samples and reported nominally significant associations with several loci in the HLA region (sample sizes, n = 100–400). The risk conferred by individual alleles was modest (odds ratios < 2.0). The basis for the associations could not be determined, though connections with known immune and auto‐immune abnormalities in SZ were postulated. Interest in the HLA associations has re‐emerged following several recent genome‐wide association studies (GWAS); which utilized 10‐ to 100‐fold larger samples and also identified associations on the short arm of chromosome 6. Unlike the earlier candidate gene studies, the associations are statistically significant following correction for multiple comparisons. Like the earlier studies; they have modest effect sizes, raising questions about their utility in risk prediction or pathogenesis research. In this review, we summarize the GWAS and reflect on possible bases for the associations. Suggestions for future research are discussed. We favor, in particular; efforts to evaluate local population sub‐structure as well as further evaluation of immune‐related variables in future studies. © 2013 Wiley Periodicals, Inc.
Molecular epidemiology: application of contemporary techniques to the typing of microorganisms.

Joel N. Maslow, Maury Ellis Mulligan, and Robert D. Arbeit From the Research Service, Veterans Affairs Medical Center, and the Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts; the Infectious Diseases Service, Veterans Affairs Medical Center, Long Beach, California; and the Department of Medicine, University of California, Irvine, California
Making Descriptive Use of Prospect Theory to Improve the Prescriptive Use of Expected Utility

This paper proposes a quantitative modification of standard utility elicitation procedures, such as the probability and certainty equivalence methods, to correct for commonly observed violations of expected utility. Traditionally, decision analysis assumes expected utility not only for the prescriptive purpose of calculating optimal decisions but also for the descriptive purpose of eliciting utilities. However, descriptive violations of expected utility bias utility elicitations. That such biases are effective became clear when systematic discrepancies were found between different utility elicitation methods that, under expected utility, should have yielded identical utilities. As it is not clear how to correct for these biases without further knowledge of their size or nature, most utility elicitations still calculate utilities by means of the expected utility formula. This paper speculates on the biases and their sizes by using the quantitative assessments of probability transformation and loss aversion suggested by prospect theory. It presents quantitative corrections for the probability and certainty equivalence methods. If interactive sessions to correct for biases are not possible, then the authors propose to use the corrected utilities rather than the uncorrected ones in prescriptions of optimal decisions. In an experiment, the discrepancies between the probability and certainty equivalence methods are removed by the authors' proposal.
BRCA2 arg372hispolymorphism and epithelial ovarian cancer risk

The BRCA2 372 HH genotype defined by the BRCA2 N372H nonconservative amino acid substitution polymorphism was recently reported to be associated with a small increased risk of breast cancer. We investigated whether this polymorphism was associated with ovarian cancer risk by conducting British and Australian case‐control comparisons in parallel, including a total sample of 1,121 ovarian cancer cases and 2,643 controls. There was no difference in genotype frequency between control groups from the 2 studies (p = 0.9). The HH genotype was associated with an increased risk of ovarian cancer in both studies, and the risk estimate for the pooled studies was 1.36 (95% CI 1.04–1.77, p = 0.03). There was also a suggestion that this risk may be greater for ovarian cancers of the serous subtype for both studies, with an OR (95% CI) of 1.66 (1.17–2.54) for the 2 studies combined (p = 0.005). The BRCA2 372 HH genotype appears to be associated with an increased risk of ovarian cancer of a similar magnitude to that reported for breast cancer. © 2002 Wiley‐Liss, Inc.
Pharmacokinetics of ceftizoxime in animals after parenteral dosing

The pharmacokinetic profile of ceftizoxime was studied in mice, rats, dogs, and monkeys given the drug in a single parenteral dose. The serum data after an intravenous injection were analyzed by the two-compartment open model. Cefotiam, cefmetazole, cefotaxime, and cefamandole were used as reference drugs. High concentrations of ceftizoxime were attained in the sera of all test animals and in the tissues of rats after parenteral dosing. The serum concentrations of ceftizoxime were higher than those of the other antibiotics in large animals (dogs and monkeys), but were lower in small animals (mice and rats). About 80% of ceftizoxime was excreted unchanged in the 24-h urine of all species tested. The biliary excretion of ceftizoxime was low: 3.7% in rats and 0.59% in dogs. However, therapeutically significant concentrations of ceftizoxime were found in the bile of dogs. Ceftizoxime was stable in biological fluids such as serum, urine, and tissue homogenates, but cefotaxime was unstable in rat tissue homogenates. Binding of ceftizoxime to serum protein in all species was the lowest of all the antibiotics: 31% for humans, 17% for dogs, and 32% for rats.
The Determinants of Corporate Debt Maturity Structure

According to Stiglitz (1974) and Modigliani and Miller (1958), in efficient and integrated markets, the financial management policy cannot decrease the costs of capital due to the interrelation between the different types of capital costs. Consequently, there is no gain from substituting debt for equity. However, evidence has been found against this claim, demonstrating that equity financing is related to the predictability of stock returns. For example, firms issue equity when the equity premium is low in order to time an inefficient market and reduce the cost of capital borrowing and/or to optimize capital structure together with expected returns (Baker et al., 2003). On the other hand, there is substantially less literature on debt financing. For example, according to Bosworth (1971), debt maturity is related to market conditions, such as the interest and inflation rates. Furthermore, Barclay and Smith (1995) find firms with higher information asymmetries to issue short-term debt. They determine a positive relationship between debt-maturity and dividend yield as well as a negative relationship between the maturity of debt and the term-spread (Barclay & Smith, 1995). Although the above papers provide support for the association between debt and returns, none offers information on the cost of capital borrowing at different times of debt maturity due to lack of analysis of returns data.
Mitochondrial Functions and Estrogen Receptor-dependent Nuclear Translocation of Pleiotropic Human Prohibitin 2*

Proteins with multiple cellular functions provide biological diversity to eukaryotic cells. In the current studies, we identified the mitochondrial functions of human prohibitin 2 (PHB2), which was initially identified as a repressor of estrogen-dependent transcriptional activity. The mitochondrial complex of PHB2 consists of PHB1, voltage-dependent anion channel 2, adenine nucleotide translocator 2, and the anti-apoptotic Hax-1, which is a novel binding partner for PHB2. RNA interference-mediated knockdown of PHB2 in HeLa cells resulted in caspase-dependent apoptosis through down-regulation of Hax-1 and fragmentation of mitochondria. We also found that, although PHB2 is predominantly expressed in the mitochondria of HeLa cells, it translocates to nucleus in the presence of estrogen receptor α and estradiol. Here, we first demonstrated the roles of mammalian PHB2 in mitochondria and the molecular mechanism of its nuclear targeting and showed that PHB2 is a possible molecule directly coupling nuclear-mitochondrial interaction.
Elastic Modulus of Cetacean Auditory Ossicles

In order to model the hearing capabilities of marine mammals (cetaceans), it is necessary to understand the mechanical properties, such as elastic modulus, of the middle ear bones in these species. Biologically realistic models can be used to investigate the biomechanics of hearing in cetaceans, much of which is currently unknown. In the present study, the elastic moduli of the auditory ossicles (malleus, incus, and stapes) of eight species of cetacean, two baleen whales (mysticete) and six toothed whales (odontocete), were measured using nanoindentation. The two groups of mysticete ossicles overall had lower average elastic moduli (35.2 ± 13.3 GPa and 31.6 ± 6.5 GPa) than the groups of odontocete ossicles (53.3 ± 7.2 GPa to 62.3 ± 4.7 GPa). Interior bone generally had a higher modulus than cortical bone by up to 36%. The effects of freezing and formalin‐fixation on elastic modulus were also investigated, although samples were few and no clear trend could be discerned. The high elastic modulus of the ossicles and the differences in the elastic moduli between mysticetes and odontocetes are likely specializations in the bone for underwater hearing. Anat Rec, 297:892–900, 2014. © 2014 Wiley Periodicals, Inc.
A gut (microbiome) feeling about the brain

Purpose of review There is an increasing realization that the microorganisms which reside within our gut form part of a complex multidirectional communication network with the brain known as the microbiome-gut-brain axis. In this review, we focus on recent findings which support a role for this axis in modulating neurodevelopment and behavior. Recent findings A growing body of research is uncovering that under homeostatic conditions and in response to internal and external stressors, the bacterial commensals of our gut can signal to the brain through a variety of mechanisms to influence processes such neurotransmission, neurogenesis, microglia activation, and modulate behavior. Moreover, the mechanisms underlying the ability of stress to modulate the microbiota and also for microbiota to change the set point for stress sensitivity are being unraveled. Dysregulation of the gut microbiota composition has been identified in a number of psychiatric disorders, including depression. This has led to the concept of bacteria that have a beneficial effect upon behavior and mood (psychobiotics) being proposed for potential therapeutic interventions. Summary Understanding the mechanisms by which the bacterial commensals of our gut are involved in brain function may lead to the development of novel microbiome-based therapies for these mood and behavioral disorders.
Galactolipid synthesis in chloroplast inner envelope is essential for proper thylakoid biogenesis, photosynthesis, and embryogenesis

The biogenesis of thylakoid membranes, an indispensable event for the photoautotrophic growth of plants, requires a significant increase in the level of the unique thylakoid membrane lipid monogalactosyldiacylglycerol (MGDG), which constitutes the bulk of membrane lipids in chloroplasts. The final step in MGDG biosynthesis occurs in the plastid envelope and is catalyzed by MGDG synthase. Here we report the identification and characterization of an Arabidopsis mutant showing a complete defect in MGDG synthase 1. The mutant seeds germinated as small albinos only in the presence of sucrose. The seedlings lacked galactolipids and had disrupted photosynthetic membranes, leading to the complete impairment of photosynthetic ability and photoautotrophic growth. Moreover, invagination of the inner envelope, which is not seen in mature WT chloroplasts, was observed in the mutant, supporting an old hypothesis that envelope invagination is a major event in early chloroplast biogenesis. In addition to the defective seedling phenotype, embryo development was arrested in the mutant, although seeds with impaired embryos could germinate heterotrophically. These results demonstrate the importance of galactolipids not only in photosynthetic growth but also in embryogenesis.
The laminar distribution of intracortical fibers originating in the olfactory cortex of the rat

In this study, the autoradiographic method for tracing axonal connections was used to identify the laminar distribution of intracortical fibers originating in the olfactory cortical areas of the rat. Most of the projections can be divided into two major fiber systems with different laminar patterns of termination. The first of these, termed the layer Ib fiber system, arises in the anterior olfactory nucleus, the anterior and posterior piriform cortex, and the lateral entorhinal cortex, and terminates predominantly in layer Ib and, in many cases, layer III of the entire olfactory cortex. The second system, termed the layer II‐deep Ib fiber system, originates in three relatively small olfactory cortical areas‐the dorsal peduncular cortex, the ventral tenia tecta, and the periamygdaloid cortex and terminates in and around the cells of layer II in most parts of the olfactory cortex. There is significant overlap in the laminar distribution of the two systems, although the distinction between them is readily apparent.
Risk factors for pertussis in adults and teenagers in England

SUMMARY Pertussis is a vaccine-preventable respiratory infection caused by Bordetella pertussis which can be fatal in infants. Although high vaccine coverage led to prolonged disease control in England, a national outbreak of pertussis in 2011 led to the largest increase in over two decades, including a marked increase in cases aged ⩾15 years. A case-control study in four regions of England was undertaken to investigate risk factors for pertussis in adolescents and adults, specifically employment type and professional and household contact with children. Pertussis cases were laboratory-confirmed and aged ⩾15 years. Controls were recruited through general practitioner nomination. Demographic and risk factor information were collected using an online survey. Multivariable logistic regression was used to estimate independent associations with outcome. Two hundred and thirty-one cases and 190 controls were recruited. None of the four employment variables (social care, education, health sector, patient contact) were significantly associated with pertussis. Professional contact with children aged < 1 year was associated with a significantly reduced odds of pertussis [odds ratio (OR) 0·25, 95% confidence interval (CI) 0·08–0·78, P = 0·017]. Household contact with ⩾1 child aged 10–14 years was associated with significantly increased odds of pertussis (OR 2·61, 95% CI 1·47–4·64, P = 0·001). Occupational contact with very young children was associated with reduced odds of pertussis, probably due to immune boosting by low-level exposures to B. pertussis. Sharing a household with a young adolescent was a significant risk factor for pertussis in adults and older teenagers. The primary focus of the childhood pertussis vaccination programmes is to prevent infant disease. Although evidence is emerging that adolescent vaccination does not provide indirect protection to infants, our results highlight the importance of children aged 10–14 years in pertussis transmission to older adolescents and adults.
The PGC-1-related Protein PERC Is a Selective Coactivator of Estrogen Receptor α*

Peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) is a tissue-specific coactivator that enhances the activity of many nuclear receptors and coordinates transcriptional programs important for energy metabolism. We describe here a novel PGC-1-related coactivator that is expressed in a similar tissue-specific manner as PGC-1, with the highest levels in heart and skeletal muscle. In contrast to PGC-1, the new coactivator shows high receptor specificity. It enhances potently the activity of estrogen receptor (ER) α, while having only small effects on other receptors. Because of its nuclear receptor selectivity, we have termed the new protein PERC (PGC-1 related EstrogenReceptor Coactivator). We show here that the coactivation function of PERC relies on a bipartite transcriptional activation domain and two LXXLL motifs that interact with the AF2 domain of ERα in an estrogen-dependent manner. PERC and PGC-1 are likely to have different functions in ER signaling. Whereas PERC acts selectively on ERα and not on the second estrogen receptor ERβ, PGC-1 coactivates strongly both ERs. Moreover, PERC and PGC-1 show distinct preferences for enhancing ERα in different promoter contexts. Finally, PERC enhances the ERα-mediated response to the partial agonist tamoxifen, while PGC-1 modestly represses it. The two coactivators are likely to mediate distinct, tissue-specific responses to estrogens.
Bone marrow‐derived cells contribute to regeneration of injured prostate epithelium and stroma

Recent studies have reported that bone marrow‐derived cells (BMDCs), which are recruited to sites of tissue injury and inflammation, can differentiate into epithelial cells, such as liver, lung, gastrointestinal tract, and skin cells. We investigated the role of BMDCs in contributing to regeneration of injured prostate epithelium.