Miracle-dz/UniFAR-FTUs huggingface dataset:
The adverse effect of obesity/high fat diet on oocyte quality and metabolism is not reversible with resumption of regular diet in mice

Obesity, which affects over one-third of reproductive-age women, has negative effects on reproduction and results in oocyte defects in both mice and humans. In this study, we used a mouse model to examine whether the adverse effects of an obesogenic diet, specifically abnormal oocyte spindle formation, mitochondrial metabolism, and lipid accumulation, can be reversed by return to normal weight and metabolic profile. Female C57BL6/J mice were placed on either a high-fat diet (HFD; 35.8% fat and 20.2% protein by nutritional content) or an isocaloric control diet (CD; 13% fat and 25% protein) for six weeks. All mice were then maintained on CD for eight weeks. We found that whereas metabolic parameters (weight, glucose tolerance, and cholesterol levels) of the HFD mice returned to normal after this “diet reversal” period, several oocyte defects were not reversible. Oocytes from the diet reversal mice demonstrated a significantly higher percentage of abnormal meiotic spindles than those from control mice. The HFD diet reversal GV oocytes also had lower mitochondrial membrane potential, lower levels of ATP and citrate, and higher percentages of abnormal lipid accumulation and distribution and abnormally distributed mitochondria than oocytes from control mice. Thus, despite normalization of weight, glucose utilization, and cholesterol levels eight weeks after switching from a high fat to a regular chow, oocytes from diet reversal mice exhibited significantly higher rates of meiotic spindle, lipid, and mitochondrial defects than found in mice maintained on regular chow. These results suggest that the negative effects of an obesogenic diet on oocyte quality are not as reversible as the overall metabolic parameters. These data may provide better insight when counseling obese women regarding reproductive options and success.
Combination of alpha-glucosidase inhibitor and ribavirin for the treatment of Dengue virus infection in vitro and in vivo

Cellular α -glucosidases I and II are enzymes that sequentially trim the three terminal glucoses in the N-linked oligosaccharides of viral envelope glycoproteins. This process is essential for the proper folding of viral glycoproteins and subsequent assembly of many enveloped viruses, including dengue virus (DENV). Imino sugars are substrate mimics of α -glucosidases I and II. In this report, we show that two oxygenated alkyl imino sugar derivatives, CM-9-78 and CM-10-18, are potent inhibitors of both α -glucosidases I and II in vitro and in treated animals, and efficiently inhibit DENV infection of cultured human cells. Pharmacokinetic studies reveal that both compounds are well tolerated at doses up to 100mg/kg in rats and have favorable pharmacokinetic properties and bioavailability in mice. Moreover, we showed that oral administration of either CM-9-78 or the peak viremia of in mice. while of mice did not the viremia, combination therapy of ribavirin with sub-effective dose of CM-10-18 demonstrated a significantly enhanced antiviral activity, as indicated by a profound reduction of the viremia. Our findings thus suggest that combination therapy of two broad-spectrum antiviral agents may provide a practically useful approach for the treatment of DENV infection.
Genome-wide Responses to Mitochondrial Dysfunction h V

Mitochondrial dysfunction can lead to diverse cellular and organismal responses. We used DNA microarrays to characterize the transcriptional responses to different mitochondrial perturbations in Saccharomyces cerevisiae . We examined respiratory-deﬁcient petite cells and respiratory-compe-tent wild-type cells treated with the inhibitors of oxidative phosphorylation antimycin, carbonyl cyanide m -chlorophenylhydrazone, or oligomycin. We show that respiratory deﬁciency, but not inhibition of mitochondrial ATP synthesis per se, induces a suite of genes associated with both peroxisomal activities and metabolite-restoration (anaplerotic) pathways that would mitigate the loss of a complete tricarboxylic acid cycle. The array data suggested, and direct microscopic observation of cells expressing a derivative of green ﬂuorescent protein with a peroxisomal matrix-targeting signal conﬁrmed, that respiratory deﬁciency dramatically induces peroxisome biogenesis. Transcript proﬁling of cells harboring null alleles of RTG1, RTG2, or RTG3 , genes known to control signaling from mitochondria to the nucleus, suggests that there are multiple pathways of cross-talk between these organelles in yeast.
Response to Pneumococcal Polysaccharide and Protein-Conjugate Vaccines Singly or Sequentially in Adults who have Recovered from Pneumococcal Pneumonia

Background— Controversy persists over the benefits of pneumococcal polysaccharide vaccine (PPV) in at-risk adults. We studied PPV, protein-conjugate pneumococcal vaccine (PCV), or immunologic ‘priming’ with PCV followed by ‘boosting’ with PPV in adults who recovered from pneumococcal pneumonia. Methods— Subjects received PPV followed in 6 months by PCV, or vice-versa. IgG to capsular polysaccharide and opsonophagocytic killing activity (OPK) were studied at baseline, 4–8 weeks and 6 months after each vaccination. Results— PPV and PCV stimulated similar IgG levels and OPK at 4–8 weeks. Six months post-PPV, antibody declined to baseline but remained modestly elevated post-PCV. PCV given 6 months post-PPV stimulated modest IgG increases that failed to reach post-PPV peaks. In contrast, PPV 6 months after PCV caused dramatic increases in IgG and OPK to all polysaccharides, consistent with a booster effect. Six months after the second vaccination, however, IgG and OPK in all patients fell precipitously, returning toward original baseline levels. Conclusions— In high-risk subjects, the effect of PPV is a more prolonged rapidly thereafter, consistent with induction of suppressor cells or tolerance. Protein vaccines may be needed for high-risk adults.
Endosomal Trafficking of the Ligated Fc ε RI Receptor

In addition to initiating signaling cascades leading to mast cell mediator release, aggregation of the high affinity IgE receptor (Fc ε RI) leads to rapid internalization of the cross-linked receptor. However, little is known about the trafficking of the internalized Fc ε RI. Here we demonstrate that in RBL-2H3 cells, aggregated Fc ε RI appears in the early endosomal antigen 1 (EEA1 + ) domains of the early endosomes within 15 minutes after ligation. Minimal co-localization of Fc ε RI with Rab5 was observed by 30 minutes, followed by its appearance in the Rab7 + late endosomes and lysosomes at later time points. During endosomal sorting, Fc ε RI α and γ subunits remain associated. In Syk-deficient RBL-2H3 cells, the rate of transport to lysosomes is markedly increased. Taken together, our data demonstrate time-dependent sorting of aggregated Fc ε RI within the endosomal-lysosomal network, and that Syk may play an essential role in regulating the trafficking and retention of Fc ε RI in endosomes.
Bidirectional Effects Between Parenting Practices and Child Externalizing Behavior: A Cross-Lagged Panel Analysis in the Context of a Psychosocial Treatment and 3-Year Follow-Up

In the current study, we examined longitudinal changes in, and bidirectional effects between, parenting practices and child behavior problems in the context of a psychosocial treatment and 3-year follow-up period. The sample comprised 139 parent-child dyads (child ages 6–11) who participated in a modular treatment protocol for early-onset ODD or CD. Parenting practices and child behavior problems were assessed at six time-points using multiple measures and multiple reporters. The data were analyzed using cross-lagged panel analyses. Results indicated robust temporal stabilities of parenting practices and child behavior problems, in the context of treatment-related improvements, but bidirectional effects between parenting practices and child behavior were less frequently detected. Our findings suggest that bidirectional effects are relatively smaller than the temporal stability of each construct for school-age children with ODD/ CD and their parents, following a multi-modal clinical intervention that is directed at both parents and children. Implications for treatment and intervention are discussed.
NHLBI Workshop Progress and New Directions in Genetics of Tuberculosis An NHLBI Working Group Report

Tuberculosis (TB), along with AIDS and malaria, is one of the three major killers among infectious diseases. New approaches to pre-venting, diagnosing, and curing TB are needed, which depend on a better understanding of Mycobacterium tuberculosis and the host. The National Heart, Lung, and Blood Institute convened a working group to develop recommendations for future TB research, including genetic aspects of the disease. The following areas were identi- fied: ( 1 ) animalmodel research toimprove understanding of persistence, reactivation, and granulomatous reactions; ( 2 ) preclinical studies aimed at shortening treatment of TB; ( 3 ) new resources for manipulating and characterizing the M. tuberculosis genome, proteome chips for more specific diagnoses, and studies of genes that appear to be essential but whose functions are not known; ( 4 ) prospective studies associated with clinical trials in populations with or at risk of TB to advance development of diagnostics and prognostics; ( 5 ) new quantitative and bioinformatic approaches to study the interaction between M. tuberculosis and the infected host and how this influences the infection process; ( 6 ) molecular characterization of M. tuberculosis genome diversity and phylogenetic analysis; ( 7 ) coordinated studies of human genome scans; ( 8 ) genetic epidemiology studies; ( 9 ) activities to foster knowledge dis- semination, education, and training; and ( 10 ) coordination between the National Institutes of Health, the Gates Foundation, the Global Alliance for Tuberculosis Drug Development, and other organizations
Higher order lumped element absorptive low‐pass and bandpass filter structures

Here, the authors present a class of lumped-element low-pass and bandpass absorptive filter circuits. To begin with, the authors discuss a new type of absorptive low-pass filter (LPF) structure that has an excellent impedance matching performance in both passband and stopband. This work provides low-pass prototype values for the proposed absorptive LPFs in terms of those for the conventional reflective filters, namely g -parameters, so that the new type of absorptive LPF can be designed in a straightforward manner. In addition, it is shown that traditional low-pass-to-bandpass frequency transformations can be applied to the absorptive low-pass prototype cases in the design of absorptive bandpass filters (BPFs). Second- and third-order LPF and BPFs are designed and measured to verify the new type of absorptive filter and its design method.
A Model of Tight Junction Function In CNS Myelinated Axons

The insulative properties of myelin sheaths in the central and peripheral nervous systems (CNS and PNS) are widely thought to derive from the high resistance and low capacitance of the constituent membranes. Although this view adequately accounts for myelin function in large diameter PNS fibers, it poorly reflects the behavior of small fibers that are prominent in many regions of the CNS. Herein, we develop a computational model to more accurately represent conduction in small fibers. By incorporating structural features that, hitherto, have not been simulated, we demonstrate that myelin tight junctions improve saltatory conduction by reducing current flow through the myelin, limiting axonal membrane depolarization and restraining the activation of ion channels beneath the myelin sheath. Accordingly, our simulations provide a novel view of myelin by which tight junctions minimize charging of the membrane capacitance and lower the membrane time constant to improve the speed and accuracy of transmission in small diameter fibers. This study establishes possible mechanisms whereby TJs affect conduction in the absence of overt perturbations to myelin architecture and may in part explain the tremor and gait abnormalities observed in Claudin 11 -null mice.
A new reidentification method for location‐based social networks

With the wide application of location‐based services and social networks, the privacy protection for both the location data and the social network data become important. There are already some methods for these two problems. This article gives a new discovery that these methods do not fit the location‐based social network (LBSN). In the LBSN, both the location and social network information can be obtained. However, most of the existing privacy protection methods only consider one of them. This article shows that privacy risk may happen when both using these two kinds of information. It is necessary to design a special privacy protection method for the LBSN. © 2018 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Cross-cultural Medicine A Decade Later Dysphoria and Somatization in Iranian Culture

Iranians express dysphoria through an undifferentiated term called narahati, meaning depressed, ill at ease, nervous, inconvenienced, or anxious. People try masking this emotion or express it in specific ways nonverbally, such as sulking or not eating. Two other dysphoric affects, sadness and anger, are not masked. Because of the social conception of persons being emotionally sensitive, the expression of narahati is guarded: expressing it not only could show that one is socially vulnerable, it could also make another sensitive empathic person narahat. The body is also sensitive, but to the physical world. Physical health is maintained by balancing a diet of "hot" and "cold" foods and avoiding exposure to cold and moisture. With the social and cultural problems brought on by revolution, war, immigration, and accommodation to a new society, Iranian refugees experience changes in family, role, status, finances, language, and other sociocultural ways of being that cause them to feel narahat and to express it verbally, nonverbally, or through somatization. Understanding Iranian conceptions of emotional and physical sensitivity will help clinicians in treating Iranian patients. (Pliskin Cross-cultural Medicine-A Decade Later [Special Issue]. West J Med 1992 Sep; 157:295-300)
Technical Advance Single-Channel Quantitative Multiplex Reverse Transcriptase-Polymerase Chain Reaction for Large Numbers of Gene Products Differentiates Nondemented from Neuropathological Alzheimer’s Disease

Effective approaches using array technologies are critical to understand the molecular bases of human diseases. The results obtained using such procedures require analysis and validation procedures that are still under development. In the context of Alzheimer’s disease, in which the identification of molecular mechanisms of underlying pathologies is vital, we describe a robust assay that is the first real-time reverse transcriptase-polymerase chain reaction-based high-throughput approach that can simultaneously quantitate the expression of a large number of genes at the copy number level from a minute amount of starting material. Using this approach within the human brain, we were able to quantitate as many as 19 genes at a time with only one type of fluorescent probe. The number of genes included can be consid-erably increased. Examples of consistent changes in Alzheimer’s disease within these 19 candidate genes included reductions in targets related to the dendritic and synaptic apparatus. These changes were specific to Alzheimer’s disease when compared with Parkinson’s disease cases. We also present comparison data with microarray analysis from the same brain region and the same patients. The high sensitivity and reproducibility of this technology coupled with appropriate multivariate analysis is proposed here to form a biotechnology platform that can be widely used for diagnostic purposes as well as basic research. (Am Simultaneous quantitation of numerous transcripts extracted from a defined tissue sample provides fundamental information for molecular neurobiology. Within identi-fied states of a disease, such information helps the understanding of molecular cascades underlying pathologies. In the present work, our objective was to develop and validate a technology that would allow the coincident expression profiling and analysis of a large number of genes at the copy number level
A Prospective Study of Peritransplant Sorafenib for Patients with FLT3-ITD Acute Myeloid Leukemia Undergoing Allogeneic Transplantation

FLT3-ITD-mutated acute myeloid leukemia (AML) remains a therapeutic challenge. FLT3 inhibition in the setting of minimal residual disease and a new immune system via allogeneic transplantation offers a promise of improved survival for these patients. We performed a prospective study of patients with FLT3-ITD AML undergoing allogeneic transplant that was conducted to evaluate the safety, tolerability, and outcome of sorafenib administered peritransplant. Sorafenib dosing was individualized, starting at 200 mg twice a day (BID), and titrated based on tolerability or toxicities until a tolerable dose was identified. Forty-four patients, with a median age of 52 years, undergoing allogeneic transplant were started on sorafenib in the peritransplant period (21 pretransplant). The median duration of post-transplant follow-up was 27.6 months (range, 5.2 to 60.4). Overall survival was 76% at both 24 and 36 months. Event-free survival at 24 and 36 months was 74% and 64%, respectively. Ten patients died in the post* transplant period, with 6 deaths due to relapsed leukemia and 4 from transplant-associated toxicity. Tolerable doses ranged from 200 mg every other day to 400 mg BID with similar exposure. Correlative studies evaluating FLT3 inhibition via a plasma inhibitory activity assay showed consistent inhibition of FLT3 at all tolerability-determined dosing levels. Sorafenib is well tolerated in the peritransplant setting irrespective of the conditioning intensity or the donor source. Our findings indicate that sorafenib dosing can be individualized in the post-transplantation setting according to patient tolerability. This approach results in effective in vivo FLT3 inhibition and yields encouraging survival results.
The effects of A. pyogenes on endometrial function in vitro, and on uterine and ovarian function in vivo

Uterine bacterial infection after parturition causes endometritis, perturbs ovarian function and leads to infertility in cattle. Although endometritis is caused by mixed infections, endometrial pathology is associated with the presence of Arcanobacterium pyogenes. The aims of the present study were to determine the effects of A. pyogenes on endometrial function in vitro, and on uterine and ovarian function in vivo. Heat-killed A. pyogenes did not affect the production of prostaglandin F 2 α (PGF) or prostaglandin E 2 (PGE) from endometrial explants, or purified populations of endometrial epithelial or stromal cells. However, the explants produced more PGF and PGE than controls when treated with a bacteria-free filtrate (BFF) cultured from A. pyogenes. Similarly, BFF stimulated PGF and PGE production by epithelial and stromal cells, respectively. So, BFF or control PBS was infused into the uterus of heifers (n = 7 per group) for 8 days, starting the day after estrus. Emergence of the follicle wave, dominant follicle or corpus luteum diameter, and peripheral plasma FSH, LH, estradiol, progesterone, PGFM, or acute phase protein concentrations were unaffected by the BFF infusion. In the live animal it is likely that the intact uterine mucosa limits the exposure of the endometrial cells to the exotoxin of A. pyogenes, whereas the cells are readily exposed to the toxin in vitro.
GM2-Gangliosidosis BI Variant: Analysis of I-Hexosaminidase a Gene Abnormalities in Seven Patients

Summary A single nucleotide transition within exon 5 of the 1-hexosaminidase a chain gene was identified in a Puerto Rican patient with GM2-gangliosidosis B1 variant as the mutation responsible for the unusual enzymological characteristics of this variant (Gs33--'A; Arg178--'His) (the DN-allele). A total of seven patients with enzymological characteristics of B1 variant have since been studied. They were Puerto Rican (DN), Italian, French, Spanish, two patients of mixed ethnic origin (English/Italian/Hungarian and En-glish/French/Azores), and a Czechoslovakian. In confirmation of our earlier finding based on screening with allele-specific probes, all patients except the one from Czechoslovakia carried the same DN-allele. A new point mutation found in this patient changed the same codon affected in the DN-allele (C532*T; Argl78-Cys). An asymptomatic Japanese individual included as a control also carried one allele with the DN-mutation. Site-directed mutagenesis and expression studies in COS I cells demonstrated that either of the two point mutations abolishes the catalytic activity of the a subunit. The Spanish patient was homozygous for the DN-allele, but others were all compound heterozygotes. The Puerto Rican patient was a compound heterozygote with the DN-mutation in one allele and with the four-base insertion in exon 11, one of the two mutations found in the classical Ashkenazi Jewish Tay-Sachs disease, in the other allele. Abnormalities of the other allele were not identified in all other compound heterozygous patients. In these patients, the level of mRNA derived from the other allele was variable, ranging from being undetectable to being much lower than normal. This series of studies uncovered a new B1 variant mutation, confirmed our preliminary finding that the DN-allele has a surprisingly wide geographic and ethnic distribution, and pointed out the highly complex nature of the molecular genetics of this rare disorder. They also support our working hypothesis that mutations responsible for the unique enzymological characteristics of the B1 variant should be located in or near exon 5 of the gene and that this region of the enzyme protein is critical for its catalytic function.
Static voltage sharing technology of multi‐break mechanical switch for hybrid HVDC breaker

The hybrid high-voltage direct current (HVDC) breaker combines mechanical and power electronics switching that enables it to interrupt power flows within a few milliseconds. Mechanical switch is a key component of hybrid HVDC breaker and has a number of serially connected interrupter units which ideally would divide the voltage equally. The static voltage distribution characteristics and voltage sharing design of a multi-break mechanical switch were discussed in this study. A finite-element model was developed to study the static voltage distribution characteristics and capacitance parameters of multi-break mechanical switch (which actually consists of resistance and capacitance parameters under direct current) as a preliminary study. Comparisons were made under the simulation of vertical and U-shaped arrangement forms. The results indicate that the static voltage distribution of the high-voltage terminal is at least more than 65%, whereas the severe non-uniform voltage distribution can be well improved by means of the method proposed in this study.