Miracle-dz/UniFAR-FTUs huggingface dataset:
Potential shortfall of pyramided transgenic cotton for insect resistance management

To delay evolution of pest resistance to transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt), the “pyramid” strategy uses plants that produce two or more toxins that kill the same pest. In the United States, this strategy has been adopted widely, with two-toxin Bt cotton replacing one-toxin Bt cotton. Although two-toxin plants are likely to be more durable than one-toxin plants, the extent of this advantage depends on several conditions. One key assumption favoring success of two-toxin plants is that they kill insects selected for resistance to one toxin, which is called “redundant killing. ” Here we tested this assumption for a major pest, Helicoverpa zea, on transgenic cotton producing Bt toxins Cry1Ac and Cry2Ab. Selection with Cry1Ac increased survival on two-toxin cotton, which contradicts the assumption. The concentration of Cry1Ac and Cry2Ab declined during the growing season, which would tend to exacerbate this problem. Furthermore, analysis of results from 21 selection experiments with eight species of lepidopteran pests indicates that some cross-resistance typically occurs between Cry1A and Cry2A toxins. Incorporation of empirical data into simulation models shows that the observed deviations from ideal conditions could greatly reduce the benefits of the pyramid strategy for pests like H. zea, which have inherently low susceptibility to Bt toxins and have been exposed extensively to one of the toxins in the pyramid before two-toxin plants are adopted. For such pests, the pyramid strategy could be improved by incorporating empirical data on deviations from ideal assumptions about redundant killing and cross-resistance.
Determination of Sex by Shape and Size of Hyoid Bone

Identification is the task that an investigator does when an unknown dead body is found with an allegation of crime. Identification is often a difficult task in many of the criminal cases due to decomposition by the time the dead body has been noticed. The present study was conducted to know the relationship of the sex with the shape and size of the hyoid bone. Excised hyoid bones from 81 male and 49 female dead bodies were studied from a South Indian population. Results showed that hyoid bones were highly polymorphic in size and shape across the ages in both sexes. However V shaped hyoid bone was more common compared to U shaped hyoid bone in adult males. The Length and the width of the hyoid bone were larger in males compared to females. The study of hyoid bone will be inadequate in sex determination and needs to be considered along with the measurements of other bones of the same individual for more accuracy.
Controlled Assembly of Biocompatible Metallic Nanoaggregates Using a Small Molecule Crosslinker

By introducing a capping step and controlling the reaction parameters, assembly of metallic nanoparticle aggregates can be achieved using a small-molecule crosslinker. Aggregates can be assembled from particles of varied size and composition and the size of the aggregates can be systematically adjusted. Following cell uptake of 60 nm aggregates, the aggregates are stable and nontoxic to macrophage cells up to 55 × 10(-3) m Au.
Conditionals by inversion provide a universal method for the generation of conditional alleles

Significance We describe conditional by inversion (COIN), a new design for conditional alleles that uses an optimized conditional gene trap module (COIN module) inserted into the target gene in an orientation opposite to the gene’s direction of transcription. Activation by Cre recombinase inverts the COIN module, resulting in expression of a reporter and termination of transcription, thereby inactivating the target gene while marking the cells where the conditional event has occurred. Creation of COIN alleles for more than 20 genes showed that it is a robust and universal method—applicable to any gene regardless of exon–intron structure—that overcomes the limitations of previous conditional approaches. Conditional mutagenesis is becoming a method of choice for studying gene function, but constructing conditional alleles is often laborious, limited by target gene structure, and at times, prone to incomplete conditional ablation. To address these issues, we developed a technology termed conditionals by inversion (COIN). Before activation, COINs contain an inverted module (COIN module) that lies inertly within the antisense strand of a resident gene. When inverted into the sense strand by a site-specific recombinase, the COIN module causes termination of the target gene’s transcription and simultaneously provides a reporter for tracking this event. COIN modules can be inserted into natural introns (intronic COINs) or directly into coding exons as part of an artificial intron (exonic COINs), greatly simplifying allele design and increasing flexibility over previous conditional KO approaches. Detailed analysis of over 20 COIN alleles establishes the reliability of the method and its broad applicability to any gene, regardless of exon–intron structure. Our extensive testing provides rules that help ensure success of this approach and also explains why other currently available conditional approaches often fail to function optimally. Finally, the ability to split exons using the COIN’s artificial intron opens up engineering modalities for the generation of multifunctional alleles.
beta-Catenin mediates adriamycin-induced albuminuria and podocyte injury in adult mouse kidneys.

BACKGROUND Glomerular slit diaphragm (SD) represents a modified adherens junction composed of molecules belonging to both immunoglobulin and cadherin superfamilies. Cadherins associate with the cytosolic scaffolding protein beta-catenin, but the precise role of beta-catenin in mature or injured podocytes is not known. METHODS The conditional podocyte-specific beta-catenin-deficient mouse line was generated using the doxycycline-inducible Cre-loxP system. Expression of the beta-catenin-deficient gene was turned off at the age of 8 weeks by doxycycline treatment and the kidney phenotype was analysed. In addition, beta-catenin-deficient and control mice were treated with adriamycin (ADR) and analysed for albuminuria and morphological alterations. RESULTS Deletion of beta-catenin in mature podocytes did not change the morphology of podocytes nor did it lead to albuminuria. However, lack of beta-catenin attenuated albuminuria after ADR treatment. Electron microscopic examination showed increased podocyte foot process effacement associated with SD abnormalities in ADR-treated control mice compared to beta-catenin-deficient mice. CONCLUSIONS These results show that beta-catenin in podocytes is dispensable for adult mice, but appears to be important in modulating the SD during ADR-induced perturbation of the filtration barrier.
Fast neurotransmitter release regulated by the endocytic scaffold intersectin

Sustained fast neurotransmission requires the rapid replenishment of release-ready synaptic vesicles (SVs) at presynaptic active zones. Although the machineries for exocytic fusion and for subsequent endocytic membrane retrieval have been well characterized, little is known about the mechanisms underlying the rapid recruitment of SVs to release sites. Here we show that the Down syndrome-associated endocytic scaffold protein intersectin 1 is a crucial factor for the recruitment of release-ready SVs. Genetic deletion of intersectin 1 expression or acute interference with intersectin function inhibited the replenishment of release-ready vesicles, resulting in short-term depression, without significantly affecting the rate of endocytic membrane retrieval. Acute perturbation experiments suggest that intersectin-mediated vesicle replenishment involves the association of intersectin with the fissioning enzyme dynamin and with the actin regulatory GTPase CDC42. Our data indicate a role for the endocytic scaffold intersectin in fast neurotransmitter release, which may be of prime importance for information processing in the brain.
Intact sphingomyelin biosynthetic pathway is essential for intracellular transport of influenza virus glycoproteins

Cells genetically deficient in sphingomyelin synthase-1 (SGMS1) or blocked in their synthesis pharmacologically through exposure to a serine palmitoyltransferase inhibitor (myriocin) show strongly reduced surface display of influenza virus glycoproteins hemagglutinin (HA) and neuraminidase (NA). The transport of HA to the cell surface was assessed by accessibility of HA on intact cells to exogenously added trypsin and to HA-specific antibodies. Rates of de novo synthesis of viral proteins in wild-type and SGMS1-deficient cells were equivalent, and HA negotiated the intracellular trafficking pathway through the Golgi normally. We engineered a strain of influenza virus to allow site-specific labeling of HA and NA using sortase. Accessibility of both HA and NA to sortase was blocked in SGMS1-deficient cells and in cells exposed to myriocin, with a corresponding inhibition of the release of virus particles from infected cells. Generation of influenza virus particles thus critically relies on a functional sphingomyelin biosynthetic pathway, required to drive influenza viral glycoproteins into lipid domains of a composition compatible with virus budding and release.
TNFα-induced IP3R1 expression through TNFR1/PC-PLC/PKCα and TNFR2 signalling pathways in human mesangial cell.

BACKGROUND Little information is available regarding the mechanisms involved in cytokine-induced type 1 inositol 1,4,5-trisphosphate receptor (IP(3)R1) expression in human mesangial cells (HMCs) in the occurrence of hepatorenal syndrome (HRS). Over-expression of IP(3)R1 would enhance both IP(3)-binding activity and sensitivity. We hypothesize that it is possible that increased IP(3)R1, induced by TNFα, would lead to increased IP(3) sensitivity in response to a variety of vasoconstrictors, and promote HMC contraction and thus lead to reduced GFP, promoting HRS occurrence and development. METHODS Quantitative real-time polymerase chain reaction and immunoblot assay were used to examine the effects of TNFα on IP(3)R1 mRNA and protein expression. Several inhibitors of kinases, depletion PKC, over-expression of dominant-negative mutant of PKC and non-radioactive PKC assay were used to examine the mechanism of signal transduction of TNFα-regulated IP(3)R1 in HMCs. RESULTS TNFα increased IP(3)R1 mRNA and protein expression in HMCs, an effect that was blocked by prolonged incubated chronic PMA, D609, safingol and also by transfection with domain-negative PKCα construct. TNFα activated and promoted autophosphorylation of the PKCα. In addition, both anti-TNFR1 and anti-TNFR2 antibodies blocked TNFα-induced IP(3)R1 protein expression, while only anti-TNFR1 antibodies but not anti-TNFR2 antibodies attenuated TNFα-induced PKCα activity. CONCLUSIONS TNFα increased the expression of IP(3)R1, and this was mediated, at least in part, through the TNFR1/PC-PLC/PKCα and TNFR2 signalling pathways in HMCs.
Salivary testosterone for the diagnosis of androgen deficiency in end-stage renal disease.

BACKGROUND Hypogonadism is frequent in patients with end-stage renal disease (ESRD). Salivary testosterone (Sal-T) is a non-invasive tool to screen androgen deficiency in adult male with normal renal function. However, available data on its utility in ESRD are not conclusive. OBJECTIVES The objectives of the study were: (i) to compare free testosterone fractions in saliva (SAL-T) and serum (Free-T); (ii) to establish the correlation of Sal-T with circulating total (TT) and bioavailable testosterone (Bio-T); (iii) to detect androgen deficiency through Sal-T; (iv) to determine the correlation of Sal-T with clinical parameters. METHODS The study included: 60 adult ESRD men on haemodialysis (20-60 years old) with decreased libido referred from two dialysis centres; 112 eugonadic and 40 hypogonadic adult men with normal renal function as controls. Simultaneous morning saliva and serum samples were obtained for testosterone measurements by liquid RIA (SAL-T; TT). Free-T and Bio-T were calculated by the Vermeulen equation. RESULTS Sal-T (0.338±0.177 nM) and Free-T (0.338±0.165 nM) did not differ (P>0.900) in ESRD as well as in control (0.337±0.182 and 0.337±0.172 nM, respectively; P>0.900). Sal-T levels correlated positively (P<0.0001) with Free-T (r=0.95), TT (r=0.80) and Bio-T (r=0.76) in ESRD. Sal-T negatively correlated with age and years on dialytic therapy. Sal-T showed 100% sensitivity and specificity to differentiate patients with androgen deficiency (22%) from those with normal androgen levels (78%). Hypogonadism was hypergonadotrophic in 69% cases and hypogonadotrophic in 31%. CONCLUSIONS These data demonstrate the value of morning Sal-T testing as a non-invasive approach to screen androgen status in ESRD patients.
Determining scientific impact using a collaboration index

Researchers collaborate on scientific projects that are often measured by both the quantity and the quality of the resultant peer-reviewed publications. However, not all collaborators contribute to these publications equally, making metrics such as the total number of publications and the H-index insufficient measurements of individual scientific impact. To remedy this, we use an axiomatic approach to assign relative credits to the coauthors of a given paper, referred to as the A-index for its axiomatic foundation. In this paper, we use the A-index to compute the weighted sums of peer-reviewed publications and journal impact factors, denoted as the C- and P-indexes for collaboration and productivity, respectively. We perform an in-depth analysis of bibliometric data for 186 biomedical engineering faculty members and from extensive simulation. It is found that these axiomatically weighted indexes better capture a researcher’s scientific caliber than do the total number of publications and the H-index, allowing for fairer and sharper evaluation of researchers with diverse collaborative behaviors.
Nanotheranostics: Congo Red/Rutin‐MNPs with Enhanced Magnetic Resonance Imaging and H2O2‐Responsive Therapy of Alzheimer's Disease in APPswe/PS1dE9 Transgenic Mice

As nanotheranostics, Congo red/Rutin-MNPs combine the abilities of diagnosis and treatment of Alzheimer's disease (AD). The biocompatible nanotheranostics system based on iron oxide magnetic nanoparticles, with ultrasmall size and excellent magnetic properties, can specifically detect amyloid plaques by magnetic resonance imaging, realize targeted delivery of AD therapeutic agents, achieve drug controlled release by H2O2 response, and prevent oxidative stress.
Parathyroid hormone-potentiated connective tissue growth factor expression in human renal proximal tubular cells through activating the MAPK and NF-kappaB signalling pathways.

BACKGROUND Secondary hyperparathyroidism is a universal complication of chronic renal diseases. One of the pathological consequences of hyperparathyroidism is impairment of the renal interstitium and tubules. However, the molecular mechanism of renal tubular interstitial impairment induced by parathyroid hormone (PTH) remains unclear. Enhanced and prolonged expression of connective tissue growth factor (CTGF) has been associated with fibrosis and inflammation in the kidney. The purpose of this study was to investigate the effects of PTH on CTGF expression patterns in human proximal tubular cell line-HK-2 cells. METHODS We treated cells with various concentrations of PTH for the indicated periods of time in the presence or absence of the mitogen-activated protein kinase (MAPK) inhibitor (PD98059) or the NF-κB inhibitor (PDTC). RESULTS Quantitative real-time RT-PCR analysis revealed that PTH at a concentration of 10(-12)-10(-10) M increased the mRNA levels of CTGF, which was similar to the trends of CTGF protein levels detected by immunoblotting assay. Our data clearly show the ability of human proximal tubular HK-2 cells to produce CTGF after the treatment with PTH. In addition, we showed that PTH induced the phosphorylation of MAPK p42 and p44, and increased NF-κB-binding activities in the PTH-treated cells. Moreover, both PD98059 and PDTC inhibited the effect of PTH on the expression of CTGF, which strongly suggests that these pathways play important roles in the PTH-induced CTGF upregulation in renal tubular cells. CONCLUSIONS Our results indicated for the first time that PTH may enhance the expression of CTGF in human kidney proximal tubular cells, suggesting that PTH may play an important role in the fibrotic and inflammatory process that is a hallmark for progression of chronic kidney disease.
Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration

Significance Here we used a visual blue opsin to induce asymmetric signaling in a cell. The opsin recruited endogenous G proteins and allowed immune cell migration to be optically steered with directional precision. Using this approach, cellular and molecular response dynamics were quantitated to facilitate computational modeling of migration. We identified an ultrasensitive switch-like signaling response that explains how immune cells filter background fluctuations in signals and respond decisively to persistent stimuli. This approach can be widely applied to understand G-protein–coupled receptor-stimulated signaling network control of other cell behaviors and potentially to control cell movements in whole animals. There is a dearth of approaches to experimentally direct cell migration by continuously varying signal input to a single cell, evoking all possible migratory responses and quantitatively monitoring the cellular and molecular response dynamics. Here we used a visual blue opsin to recruit the endogenous G-protein network that mediates immune cell migration. Specific optical inputs to this optical trigger of signaling helped steer migration in all possible directions with precision. Spectrally selective imaging was used to monitor cell-wide phosphatidylinositol (3,4,5)-triphosphate (PIP3), cytoskeletal, and cellular dynamics. A switch-like PIP3 increase at the cell front and a decrease at the back were identified, underlying the decisive migratory response. Migration was initiated at the rapidly increasing switch stage of PIP3 dynamics. This result explains how a migratory cell filters background fluctuations in the intensity of an extracellular signal but responds by initiating directionally sensitive migration to a persistent signal gradient across the cell. A two-compartment computational model incorporating a localized activator that is antagonistic to a diffusible inhibitor was able to simulate the switch-like PIP3 response. It was also able simulate the slow dissipation of PIP3 on signal termination. The ability to independently apply similar signaling inputs to single cells detected two cell populations with distinct thresholds for migration initiation. Overall the optical approach here can be applied to understand G-protein–coupled receptor network control of other cell behaviors.
Few‐Volt Operation of Printed Organic Ferroelectric Capacitor

The fabrication of single-crystalline thin-film arrays for an organic ferroelectric small molecule is achieved by a simple solution process without additional thermal annealing. Based on a cooperative proton tautomerism through a hydrogen-bonding network, films show the polarity switching with an operating voltage of less than 5 V at room temperature. This approach provides a low-cost and eco-friendly fabrication of ferroelectric devices.
Hepatocellular Carcinoma: Epidemiology and Etiology

Davide Degli Esposti1,2, Morando Soffritti3,*, Antoinette Lemoine1,2, Eva Tibaldi3 and Marco Manservigi3 1AP-HP, Hopital Paul Brousse, Service de Biochimie et Biologie Moleculaire, Inserm; Universite Paris-Sud 11; PRES Universud-Paris; Paul Vaillant Couturier 2Laboratoire de Biochimie et Biologie Cellulaire, Faculte de Pharmacie, Universite Paris-Sud 11, Jean Baptiste Clement 3Cesare Maltoni Cancer Research Center, Ramazzini Institute, Castello di Bentivoglio, Via Saliceto, Bentivoglio, Bologna, 1,2France 3Italy
Electric Response Audiometry in Clinical Practice

Part 1 Basis of the auditory-evoked potentials: historical development of electric-response audiometry (ERA) anatomy, physiology, and classification of the generators of auditory-evoked potentials basic principles of instrumentation and signal-processing. Part 2 Clinical use of auditory-evoked potentials: electrocochleography (ECochG) ECochG in hearing disorders the auditory brainstem response (ABR) the ABR in hearing disorders and auditory dysfunction middle-latency responses (MLR) the slow vertex response (SVR) other long latency responses. Part 3 Electric-response audiometry testing strategies: comparative assessment of ERA threshold techniques ERA in hearing screening in neonates and infants ERA in the `difficult-to-test child' ERA in non-organic hearing loss (NOHL) ERA in neuro-otologic diagnosis ERA in investigation of neurological disorders monitoring auditory-evoked potentials during neuro-otologic surgery electrically evoked potentials in cochlear stimulation future developments.
Some observations on the dilution, cooling and freezing of canine semen

Canine semen was obtained by digital manipulation from two donor dogs and twelve stud dogs. The sperm-rich fraction was diluted with either of two different diluents and the survival of spermatozoa before and after freezing was determined. It appeared that there was no difference in the post-thaw survival rate in either of the diluents used.
PNAS Plus Significance Statements

Copper is essential for normal growth and development because it serves roles in catalysis, signaling, and structure. Cells acquire copper through the copper transporter 1 (Ctr1) protein, a copper transporter that localizes to the cell membrane and intracellular vesicles. Both copper and the anticancer drug cisplatin are imported by Ctr1 by virtue of an extracellular domain rich in metal-binding amino acids. In this report (pp. E4279–E4288) we demonstrate that a protein structurally related to Ctr1, called Ctr2, plays a role in the generation or stability of a truncated form of Ctr1 lacking a large portion of the extracellular domain. Retention of this domain in mice or cells lacking Ctr2 enhances copper and cisplatin uptake, thereby establishing Ctr2 as a regulator of Ctr1 function.
tRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding

tRNA modifications are crucial to ensure translation efficiency and fidelity. In eukaryotes, the URM1 and ELP pathways increase cellular resistance to various stress conditions, such as nutrient starvation and oxidative agents, by promoting thiolation and methoxycarbonylmethylation, respectively, of the wobble uridine of cytoplasmic (tKUUU), (tQUUG), and (tEUUC). Although in vitro experiments have implicated these tRNA modifications in modulating wobbling capacity and translation efficiency, their exact in vivo biological roles remain largely unexplored. Using a combination of quantitative proteomics and codon-specific translation reporters, we find that translation of a specific gene subset enriched for AAA, CAA, and GAA codons is impaired in the absence of URM1- and ELP-dependent tRNA modifications. Moreover, in vitro experiments using native tRNAs demonstrate that both modifications enhance binding of tKUUU to the ribosomal A-site. Taken together, our data suggest that tRNA thiolation and methoxycarbonylmethylation regulate translation of genes with specific codon content.
A General Method for Multimetallic Platinum Alloy Nanowires as Highly Active and Stable Oxygen Reduction Catalysts

An unconventional class of high-performance Pt alloy multimetallic nanowires (NWs) is produced by a general method. The obtained PtNi NWs exhibit amazingly specific and mass oxygen reduction reaction (ORR) activities with improvement factors of 51.1 and 34.6 over commercial Pt/C catalysts, respectively, and are also stable in ORR conditions, making them among the most efficient electrocatalysts for ORR.