Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalencia de betalactamasas de espectro extendido en Escherichia coli, Klebsiella pneumoniae y Klebsiella oxytoca del Hospital Occidente de Kennedy. Nivel III, Bogotá

El objetivo es calcular la prevalencia para Escherichia coli, Klebsiella pneumoniae y Klebsiella oxytoca, productoras de betalactamasas espectro extendido, en el Hospital Occidente de Kennedy Nivel III, de Bogota. Metodologia: se analizaron en el Hospital Occidente de Kennedy, durante el periodo comprendido entre el 20 de noviembre de 2002 y el 30 septiembre de 2003, 3.574 cultivos, en los cuales se identificaron 897 cepas de Kepsiella pneumoniae, Klebsiella oxytoca y Escherichia coli, mediante paneles de microdilucion del sistema de MicroScan Dried Gram Negative, como prueba de cribado para la identificacion de germen y susceptibilidad a betalactamasas de espectro extendido. Luego se realizo una prueba confirmatoria con paneles de sistema MicroScan Dried ESBL Confirmation, recomendada para su uso por el National Committee for Clinical Laboratory Standards (NCCLS), al evaluar la concentracion inhibitoria minima para ceftazidima y cefotaxima solos y en combinacion con acido clavulanico. Resultados: los resultados mostraron una prevalencia combinada de germenes productores betalactamasas igual a 18,6% (intervalo de confianza del 95%: 16,2%-21,4%). La prevalencia para Escherichia coli fue de 9,5%; para Klebsiella pneumoniae, de 43,5%, y para Klebsiella oxytoca, de 10,3%. Los indices de resistencia bacteriana mas altos correspondieron a ceftriaxona y ceftazidima. Conclusion: el estudio demuestra una alta prevalencia de betalactamasas de espectro extendido en germenes gramnegativos, probablemente por el uso excesivo de antibioticos betalactamicos de amplio espectro. Ademas, se destaca la importancia de la deteccion con pruebas de susceptibilidad y confirmacion, como apoyo para la instauracion de medidas de control y de vigilancia epidemiologica, con el fin de reducir indices de resistencia bacteriana emergente.
Quantitative Analysis of Synaptic Vesicle Rabs Uncovers Distinct Yet Overlapping Roles for Rab3a and Rab27b in Ca2+-Triggered Exocytosis

Rab GTPases are molecular switches that orchestrate protein complexes before membrane fusion reactions. In synapses, Rab3 and Rab5 proteins have been implicated in the exo-endocytic cycling of synaptic vesicles (SVs), but an involvement of additional Rabs cannot be excluded. Here, combining high-resolution mass spectrometry and chemical labeling (iTRAQ) together with quantitative immunoblotting and fluorescence microscopy, we have determined the exocytotic (Rab3a, Rab3b, Rab3c, and Rab27b) and endocytic (Rab4b, Rab5a/b, Rab10, Rab11b, and Rab14) Rab machinery of SVs. Analysis of two closely related proteins, Rab3a and Rab27b, revealed colocalization in synaptic nerve terminals, where they reside on distinct but overlapping SV pools. Moreover, whereas Rab3a readily dissociates from SVs during Ca2+-triggered exocytosis, and is susceptible to membrane extraction by Rab-GDI, Rab27b persists on SV membranes upon stimulation and is resistant to GDI-coupled Rab retrieval. Finally, we demonstrate that selective modulation of the GTP/GDP switch mechanism of Rab27b impairs SV recycling, suggesting that Rab27b, probably in concert with Rab3s, is involved in SV exocytosis.
The role of ADP-ribosylation in regulating DNA double-strand break repair

ADP-ribosylation is the post translational modification of proteins catalysed by ADP-ribosyltransferases (ARTs). ADP-ribosylation has been implicated in a wide variety of cellular processes including cell growth and differentiation, apoptosis and transcriptional regulation. Perhaps the best characterised role, however, is in DNA repair and genome stability where ADP-ribosylation promotes resolution of DNA single strand breaks. Although ADP-ribosylation also occurs at DNA double strand breaks (DSBs), which ARTs catalyse this reaction and the molecular basis of how this modification regulates their repair remains a matter of debate. Here we review recent advances in our understanding of how ADP-ribosylation regulates DSB repair. Specifically, we highlight studies using the genetic model organism Dictyostelium, in addition to vertebrate cells that identify a third ART that accelerates DSB repair by non-homologous end-joining through promoting the interaction of repair factors with DNA lesions. The implications of these data with regards to how ADP-ribosylation regulates DNA repair and genome stability are discussed.
Risk Factors for Early, Persistent, and Late-onset Wheezing in Young Children

Wheezing in childhood is not a single disorder and different wheezing-associated respiratory illnesses have been recently described. We investigated the association between wheezing conditions and familial, pre-, peri-, and postnatal risk factors. We studied 16,333 children, 6 to 7 yr old, enrolled in a population-based study. Standardized questionnaires were filled in by parents. A total of 1,221 children had transient early wheezing, 671 had persistent wheezing, 918 had late-onset wheezing, and 13,523 never had wheezing or asthma (control group). Maternal asthma or chronic obstructive airway disease were significantly (p 35 yr old was protective against transient early wheezing (odds ratio [OR]: 0.68, 95% confidence intervals [95% CI]: 0.53 to 0.86). Breast feeding ⩾ 6 mo was slightly protective against tran.
Ventral Tegmental Area Dopamine Cell Activation during Male Rat Sexual Behavior Regulates Neuroplasticity and d-Amphetamine Cross-Sensitization following Sex Abstinence

Experience with sexual behavior causes cross-sensitization of amphetamine reward, an effect dependent on a period of sexual reward abstinence. We previously showed that ΔFosB in the nucleus accumbens (NAc) is a key mediator of this cross-sensitization, potentially via dopamine receptor activation. However, the role of mesolimbic dopamine for sexual behavior or cross-sensitization between natural and drug reward is unknown. This was tested using inhibitory designer receptors exclusively activated by designer drugs in ventral tegmental area (VTA) dopamine cells. rAAV5/hSvn-DIO-hm4D-mCherry was injected into the VTA of TH::Cre adult male rats. Males received clozapine N-oxide (CNO) or vehicle injections before each of 5 consecutive days of mating or handling. Following an abstinence period of 7 d, males were tested for amphetamine conditioned place preference (CPP). Next, males were injected with CNO or vehicle before mating or handling for analysis of mating-induced cFos, sex experience-induced ΔFosB, and reduction of VTA dopamine soma size. Results showed that CNO did not affect mating behavior. Instead, CNO prevented sexual experience-induced cross-sensitization of amphetamine CPP, ΔFosB in the NAc and medial prefrontal cortex, and decreases in VTA dopamine soma size. Expression of hm4D-mCherry was specific to VTA dopamine cells and CNO blocked excitation and mating-induced cFos expression in VTA dopamine cells. These findings provide direct evidence that VTA dopamine activation is not required for initiation or performance of sexual behavior. Instead, VTA dopamine directly contributes to increased vulnerability for drug use following loss of natural reward by causing neuroplasticity in the mesolimbic pathway during the natural reward experience. SIGNIFICANCE STATEMENT Drugs of abuse act on the neural pathways that mediate natural reward learning and memory. Exposure to natural reward behaviors can alter subsequent drug-related reward. Specifically, experience with sexual behavior, followed by a period of abstinence from sexual behavior, causes increased reward for amphetamine in male rats. This study demonstrates that activation of ventral tegmental area dopamine neurons during sexual experience regulates cross-sensitization of amphetamine reward. Finally, ventral tegmental area dopamine cell activation is essential for experience-induced neural adaptations in the nucleus accumbens, prefrontal cortex, and ventral tegmental area. These findings demonstrate a role of mesolimbic dopamine in the interaction between natural and drug rewards, and identify mesolimbic dopamine as a key mediator of changes in vulnerability for drug use after loss of natural reward.
Statistics of the Electrosensory Input in the Freely Swimming Weakly Electric Fish Apteronotus leptorhynchus

The neural computations underlying sensory-guided behaviors can best be understood in view of the sensory stimuli to be processed under natural conditions. This input is often actively shaped by the movements of the animal and its sensory receptors. Little is known about natural sensory scene statistics taking into account the concomitant movement of sensory receptors in freely moving animals. South American weakly electric fish use a self-generated quasi-sinusoidal electric field for electrolocation and electrocommunication. Thousands of cutaneous electroreceptors detect changes in the transdermal potential (TDP) as the fish interact with conspecifics and the environment. Despite substantial knowledge about the circuitry and physiology of the electrosensory system, the statistical properties of the electrosensory input evoked by natural swimming movements have never been measured directly. Using underwater wireless telemetry, we recorded the TDP of Apteronotus leptorhynchus as they swam freely by themselves and during interaction with a conspecific. Swimming movements caused low-frequency TDP amplitude modulations (AMs). Interacting with a conspecific caused additional AMs around the difference frequency of their electric fields, with the amplitude of the AMs (envelope) varying at low frequencies due to mutual movements. Both AMs and envelopes showed a power-law relationship with frequency, indicating spectral scale invariance. Combining a computational model of the electric field with video tracking of movements, we show that specific swimming patterns cause characteristic spatiotemporal sensory input correlations that contain information that may be used by the brain to guide behavior.
Mutant α-Synuclein Overexpression Induces Stressless Pacemaking in Vagal Motoneurons at Risk in Parkinson's Disease

α-Synuclein overexpression (ASOX) drives the formation of toxic aggregates in neurons vulnerable in Parkinson's disease (PD), including dopaminergic neurons of the substantia nigra (SN) and cholinergic neurons of the dorsal motor nucleus of the vagus (DMV). Just as these populations differ in when they exhibit α-synucleinopathies during PD pathogenesis, they could also differ in their physiological responses to ASOX. An ASOX-mediated hyperactivity of SN dopamine neurons, which was caused by oxidative dysfunction of Kv4.3 potassium channels, was recently identified in transgenic (A53T-SNCA) mice overexpressing mutated human α-synuclein. Noting that DMV neurons display extensive α-synucleinopathies earlier than SN dopamine neurons while exhibiting milder cell loss in PD, we aimed to define the electrophysiological properties of DMV neurons in A53T-SNCA mice. We found that DMV neurons maintain normal firing rates in response to ASOX. Moreover, Kv4.3 channels in DMV neurons exhibit no oxidative dysfunction in the A53T-SNCA mice, which could only be recapitulated in wild-type mice by glutathione dialysis. Two-photon imaging of redox-sensitive GFP corroborated the finding that mitochondrial oxidative stress was diminished in DMV neurons in the A53T-SNCA mice. This reduction in oxidative stress resulted from a transcriptional downregulation of voltage-activated (Cav) calcium channels in DMV neurons, which led to a reduction in activity-dependent calcium influx via Cav channels. Thus, ASOX induces a homeostatic remodeling with improved redox signaling in DMV neurons, which could explain the differential vulnerability of SN dopamine and DMV neurons in PD and could promote neuroprotective strategies that emulate endogenous homeostatic responses to ASOX (e.g., stressless pacemaking) in DMV neurons. SIGNIFICANCE STATEMENT Overexpression of mutant α-synuclein causes Parkinson's disease, presumably by driving neurodegeneration in vulnerable neuronal target populations. However, the extent of α-synuclein pathology (e.g., Lewy bodies) is not directly related to the degree of neurodegeneration across various vulnerable neuronal populations. Here, we show that, in contrast to dopamine neurons in the substantia nigra, vagal motoneurons do not enhance their excitability and oxidative load in response to chronic mutant α-synuclein overexpression. Rather, by downregulating their voltage-activated calcium channels, vagal motoneurons acquire a stressless form of pacemaking that diminishes mitochondrial and cytosolic oxidative stress. Emulating this endogenous adaptive response to α-synuclein overexpression could lead to novel strategies to protect dopamine neurons and perhaps delay the onset of Parkinson's disease.
Retinoic Acid Signaling Mediates Hair Cell Regeneration by Repressing p27kip and sox2 in Supporting Cells

During development, otic sensory progenitors give rise to hair cells and supporting cells. In mammalian adults, differentiated and quiescent sensory cells are unable to generate new hair cells when these are lost due to various insults, leading to irreversible hearing loss. Retinoic acid (RA) has strong regenerative capacity in several organs, but its role in hair cell regeneration is unknown. Here, we use genetic and pharmacological inhibition to show that the RA pathway is required for hair cell regeneration in zebrafish. When regeneration is induced by laser ablation in the inner ear or by neomycin treatment in the lateral line, we observe rapid activation of several components of the RA pathway, with dynamics that position RA signaling upstream of other signaling pathways. We demonstrate that blockade of the RA pathway impairs cell proliferation of supporting cells in the inner ear and lateral line. Moreover, in neuromast, RA pathway regulates the transcription of p27kip and sox2 in supporting cells but not fgf3. Finally, genetic cell-lineage tracing using Kaede photoconversion demonstrates that de novo hair cells derive from FGF-active supporting cells. Our findings reveal that RA has a pivotal role in zebrafish hair cell regeneration by inducing supporting cell proliferation, and shed light on the underlying transcriptional mechanisms involved. This signaling pathway might be a promising approach for hearing recovery. SIGNIFICANCE STATEMENT Hair cells are the specialized mechanosensory cells of the inner ear that capture auditory and balance sensory input. Hair cells die after acoustic trauma, ototoxic drugs or aging diseases, leading to progressive hearing loss. Mammals, in contrast to zebrafish, lack the ability to regenerate hair cells. Here, we find that retinoic acid (RA) pathway is required for hair cell regeneration in vivo in the zebrafish inner ear and lateral line. RA pathway is activated very early upon hair cell loss, promotes cell proliferation of progenitor cells, and regulates two key genes, p27kip and sox2. Our results position RA as an essential signal for hair cell regeneration with relevance in future regenerative strategies in mammals.
Origin of metastases: Subspecies of cancers generated by intrinsic karyotypic variations

Conventional mutation theories do not explain (1) why the karyotypes of metastases are related to those of parental cancers but not to those of metastases of other cancers and (2) why cancers metastasize at rates that often far exceed those of conventional mutations. To answer these questions, we advance here the theory that metastases are autonomous subspecies of cancers, rather than mutations. Since cancers are species with intrinsically flexible karyotypes, they can generate new subspecies by spontaneous karyotypic rearrangements. This phylogenetic theory predicts that metastases are karyotypically related to parental cancers but not to others. Testing these predictions on metastases from two pancreatic cancers, we found: (1) Metastases had individual karyotypes and phenotypes. The karyotypes of metastases were related to, but different from, those of parental cancers in 11 out of 37 and 26 out of 49 parental chromosomal units. Chromosomal units are defined as intact chromosomes with cancer-specific copy numbers and marker chromosomes that are > 50% clonal. (2) Metastases from the two different cancers did not share chromosomal units. Testing the view that multi-chromosomal rearrangements occur simultaneously in cancers, as opposed to sequentially, we found spontaneous non-clonal rearrangements with as many new chromosomal units as in authentic metastases. We conclude that metastases are individual autonomous species differing from each other and parental cancers in species-specific karyotypes and phenotypes. They are generated from parental cancers by multiple simultaneous karyotypic rearrangements, much like new species. The species-specific individualities of metastases explain why so many searches for commonalities have been unsuccessful.
Antidiabetic effect of the aerial part ethanolic extracts of Zygophyllum geslini Coss. in streptozotocin induced-diabetic rats

Zygophyllum geslini Coss commonly called Aggaya is a zygophyllacae very widespread in the Algerian Sahara. The present study investigate the antidiabetic effect of the ethanolic extract of Z. geslini aerial part administered orally in Wistar rats rendered diabetic by the intravenous injection of 50 mg/kg of streptozotocin. The present study consists of two essential parts. The first realized over a long period was devoted to the study of the ethanolic extract effect on glycemia and body weight during five weeks. In this first series of experiments, a non significant reduction of glycemia was noticed. The second part consists of the follow-up of the variation of the glycemia after treatment by the same extract during 7 hours. A significant reduction in glycemia was observed between the second and seventh hour after administration of 1.0 g/kg ethanolic extract. This reduction can go up to 75 % of basal glycemia. Thus, the ethanolic extract at 1 g/kg is endowed with a remarkable antidiabetic activity. This extract may thus represent a natural resource of new antidiabetic substances.
Prenatal developmental toxicity studies of 1,1,1‐trichloro‐2,2‐bis(4‐methoxyphenyl)ethane (methoxychlor) in rats and rabbits

ABSTRACT The studies were conducted in rats and rabbits to elucidate the potential developmental toxicity of methoxychlor in general accordance with the improved Japanese MAFF guidelines (12‐Nousan‐No. 8147, 2–1–18, 2000). Methoxychlor dissolved in corn oil was administered orally to pregnant Jcl:SD rats on gestational days (GD) 6–19 at a dose of 0,1,50, or 150 mg/kg/day and to pregnant Kbl:JW rabbits on GD 6–27 at a dose of 0,1, 15, or 45 mg/kg/day. Maternal animals were killed on the day after the last day of administration for morphological examination of their fetuses with special attention to the reproductive organs.
Rule-based diagnostic decision aids for common eye problems

In developing countries, blindness often results from a lack of proper treatment for relatively simple eye problems. Specialist medical care is not readily available, and patients are seen by frontline health workers. To assist primary health workers in the management of common and potentially blinding eye disorders, the authors have developed a computer program for a hand-held computer that incorporates a set of guidelines for diagnosis and treatment or referral to a more distant medical center. They review the progress made in implementing, testing, and disseminating this program. They also describe progress in developing another program for automating laboratory test selection in uveitis. <<ETX>>
Tenuous Inhibitory GABAergic Signaling in the Reticular Thalamus

Maintenance of a low intracellular Cl− concentration ([Cl−]i) is critical for enabling inhibitory neuronal responses to GABAA receptor-mediated signaling. Cl− transporters, including KCC2, and extracellular impermeant anions ([A]o) of the extracellular matrix are both proposed to be important regulators of [Cl−]i. Neurons of the reticular thalamic (RT) nucleus express reduced levels of KCC2, indicating that GABAergic signaling may produce excitation in RT neurons. However, by performing perforated patch recordings and calcium imaging experiments in rats (male and female), we find that [Cl−]i remains relatively low in RT neurons. Although we identify a small contribution of [A]o to a low [Cl−]i in RT neurons, our results also demonstrate that reduced levels of KCC2 remain sufficient to maintain low levels of Cl−. Reduced KCC2 levels, however, restrict the capacity of RT neurons to rapidly extrude Cl− following periods of elevated GABAergic signaling. In a computational model of a local RT network featuring slow Cl− extrusion kinetics, similar to those we found experimentally, model RT neurons are predisposed to an activity-dependent switch from GABA-mediated inhibition to excitation. By decreasing the activity threshold required to produce excitatory GABAergic signaling, weaker stimuli are able to propagate activity within the model RT nucleus. Our results indicate the importance of even diminished levels of KCC2 in maintaining inhibitory signaling within the RT nucleus and suggest how this important activity choke point may be easily overcome in disorders such as epilepsy. SIGNIFICANCE STATEMENT Precise regulation of intracellular Cl− levels ([Cl−]i) preserves appropriate, often inhibitory, GABAergic signaling within the brain. However, there is disagreement over the relative contribution of various mechanisms that maintain low [Cl−]i. We found that the Cl− transporter KCC2 is an important Cl− extruder in the reticular thalamic (RT) nucleus, despite this nucleus having remarkably low KCC2 immunoreactivity relative to other regions of the adult brain. We also identified a smaller contribution of fixed, impermeant anions ([A]o) to lowering [Cl−]i in RT neurons. Inhibitory signaling among RT neurons is important for preventing excessive activation of RT neurons, which can be responsible for generating seizures. Our work suggests that KCC2 critically restricts the spread of activity within the RT nucleus.