Miracle-dz/UniFAR-FTUs huggingface dataset:
The American Association of Suicidology No Evidence of Suicide Increase Following Terrorist Attacks in the United States : An Interrupted Time-Series Analysis of September 11 and Oklahoma City

There is substantial evidence of detrimental psychological sequelae following disasters, including terrorist attacks. The effect of these events on extreme responses such as suicide, however, is unclear. We tested competing hypotheses about such effects by employing autoregressive integrated moving average techniques to model the impact of September 11 and the Oklahoma City bombing on monthly suicide counts at the local, state, and national level. Unlike prior studies that provided conflicting evidence, rigorous time series techniques revealed no support for an increase or decrease in suicides following these events. We conclude that while terrorist attacks produce subsequent psychological morbidity and may affect self and collective efficacy well beyond their immediate impact, these effects are not strong enough to influence levels of suicide mortality.
Comparison of phenotypic versus genotypic methods in the detection of methicillin resistance in Staphylococcus aureus.

Background & objectives: Conventional methods to detect methicillin resistance in Staphylococcus aureus are inadequate as expression of resistance is subject to environmental and conditional expression of PBP2a antigen. The objective of the present study was to determine methicillin resistance in S. aureus by conventional susceptibility (oxacillin disc diffusion and oxacillin MIC) and molecular methods (PCR) and to evaluate latex agglutination test for the detection of PBP 2a and to compare the results of these tests for its sensitivity, specificity and rapidity. Methods: A total of 150 consecutive clinical isolates of Staphylococcus aureus received at the Department of Microbiology, Christian Medical College, Vellore, were included. Oxacillin (1 mg) disc diffusion and agar dilution method were used. The isolates were also subjected to latex agglutination test for detection of PBP2a and multiplex PCR to detect mecA and femB genes. Results: Of the 150 isolates, 33 were found to be MRSA by oxacillin disc diffusion. By MIC method, 13 per cent of the isolates had values 32 mg/ml, 6 per cent between 16-8 mg/ml and 2.7 per cent had a value of 4 mg/ml; 100 per cent concordance was obtained between the oxacillin disc screening and MIC methods. The latex agglutination showed positive reaction for all MRSA with only one MSSA being falsely classified as MRSA. The specificity and sensitivity were 99 and 100 per cent respectively. Test results were obtained within 15 min. By multiplex PCR, all 22 per cent of MRSA were positive for mecA and femB genes and additionally one MSSA carried mecA gene. However, femB gene was not found in 6 MSSA isolates. Specificity and sensitivity of PCR for mecA detection was similar to latex agglutination test. PCR system required approximately five hours. Interpretation & conclusions: Our findings showed that the conventional methods for detection of methicillin resistance like disc screening, disc diffusion and MIC are cost-effective but time consuming. Latex agglutination though expensive is rapid and can be a good preliminary screen with high sensitivity and specificity. Multiplex PCR is a good confirmatory test though expensive.
Phosphorylation-mediated regulation of GEFs for RhoA

Spatio-temporal control of RhoA GTPase is critical for regulation of cell migration, attachment to extracellular matrix, and cell–cell adhesions. Activation of RhoA is mediated by guanine nucleotide exchange factors (GEFs), a diverse family of enzymes that are controlled by multiple signaling pathways regulating actin cytoskeleton and cell migration. GEFs can be regulated by different mechanisms. Growing evidence demonstrates that phosphorylation serves as one of the predominant signals controlling activity, interactions, and localization of RhoGEFs. It acts as a positive and a negative regulator, and allows for regulation of RhoGEFs by multiple signaling cascades. Although there are common trends in phosphorylation-mediated regulation of some RhoGEF homologs, the majority of GEFs utilize distinct mechanisms that are dictated by their unique structure and interaction networks. This diversity enables multiple signaling pathways to use different RhoGEFs for regulation of a single central—RhoA. Here, we review current examples of phosphorylation-mediated regulation of GEFs for RhoA and its role in cell migration, discuss mechanisms, and provide insights into potential future directions.
Fibrillin-1 and alpha8 integrin are co-expressed in the glomerulus and interact to convey adhesion of mesangial cells

Fibrillin-1 is a microfibrillar extracellular matrix protein that was described to be a ligand for α8 integrin. α8 integrin is a matrix receptor specifically expressed in mesangial and smooth muscle cells of the kidney. In previous studies we detected glomerular expression of fibrillin-1. Moreover, fibrillin-1 promoted adhesion, migration, and proliferation of mesangial cells. We hypothesized that fibrillin-1 and α8 integrin might interact in the glomerulus, and thus, regulate mesangial cell properties. Our studies showed that fibrillin-1 and α8 integrin colocalize in the glomerular mesangium. Induction of experimental glomerulonephritis led to an increase of both fibrillin-1 and α8 integrin expression. In vitro studies revealed that mesangial cells deficient for α8 integrin adhere weaker to fibrillin-1 and migrate more easily on fibrillin-1 than wild-type mesangial cells. Baseline proliferation on fibrillin-1 is higher in α8 integrin-deficient mesangial cells, but the induction of proliferation is not different in α8 integrin-deficient and wild-type mesangial cells. We conclude that fibrillin-1 and α8 integrin interact, and thus, regulate mesangial cell adhesion and migration. The concomitant induction of both fibrillin-1 and α8 integrin in a self-limited model of glomerular injury points to a protective role of the interaction of fibrillin-1 with α8 integrin in the glomerulus resulting in reduced damage of the glomerular tuft as a consequence of firm adhesion of mesangial cells.
CASE STUDY: Consumption of Toxic Fescue Impairs Bull Reproductive Parameters

Consumption of toxic endophytic tall fescue grass is associated with reduced fertility rates in livestock. In this study, Angus bulls were fed a control diet (n = 3) or toxic fescue diet (n = 3) for 60 d. Semen was collected by electro-ejaculation twice weekly and evaluated for spermatozoal motility, morphology, and concentration. Scrotal temperatures, scrotal circumferences, and rectal temperatures were measured prior to each collection. Significant differences were observed for scrotal temperatures (P<0.001), scrotal circumference (P<0.01), and spermatozoa concentration (P<0.05). Scrotal temperatures were greater, scrotal circumferences were smaller, and spermatozoal concentrations were greater in the collections from bulls fed the fescue diet. Neither sperm motility nor morphology were affected by dietary treatment; however, there appeared to be a detrimental effect associated with treatment diet by day on motility during the last 2 wk of the trial (P=0.08). These results indicate that bulls fed toxic endophyte-infected (EI )f escue may experience impaired reproductive capabilities.
Neural Processing of Risk

In our everyday life, we often have to make decisions with risky consequences, such as choosing a restaurant for dinner or choosing a form of retirement saving. To date, however, little is known about how the brain processes risk. Recent conceptualizations of risky decision making highlight that it is generally associated with emotions but do not specify how emotions are implicated in risk processing. Moreover, little is known about risk processing in non-choice situations and how potential losses influence risk processing. Here we used quantitative meta-analyses of functional magnetic resonance imaging experiments on risk processing in the brain to investigate (1) how risk processing is influenced by emotions, (2) how it differs between choice and non-choice situations, and (3) how it changes when losses are possible. By showing that, over a range of experiments and paradigms, risk is consistently represented in the anterior insula, a brain region known to process aversive emotions such as anxiety, disappointment, or regret, we provide evidence that risk processing is influenced by emotions. Furthermore, our results show risk-related activity in the dorsolateral prefrontal cortex and the parietal cortex in choice situations but not in situations in which no choice is involved or a choice has already been made. The anterior insula was predominantly active in the presence of potential losses, indicating that potential losses modulate risk processing.
Electrophysiological Evidence That the Retrosplenial Cortex Displays a Strong and Specific Activation Phased with Hippocampal Theta during Paradoxical (REM) Sleep

It is widely accepted that cortical neurons are similarly more activated during waking and paradoxical sleep (PS; aka REM) than during slow-wave sleep (SWS). However, we recently reported using Fos labeling that only a few limbic cortical structures including the retrosplenial cortex (RSC) and anterior cingulate cortex (ACA) contain a large number of neurons activated during PS hypersomnia. Our aim in the present study was to record local field potentials and unit activity from these two structures across all vigilance states in freely moving male rats to determine whether the RSC and the ACA are electrophysiologically specifically active during basal PS episodes. We found that theta power was significantly higher during PS than during active waking (aWK) similarly in the RSC and hippocampus (HPC) but not in ACA. Phase–amplitude coupling between HPC theta and gamma oscillations strongly and specifically increased in RSC during PS compared with aWK. It did not occur in ACA. Further, 68% and 43% of the units recorded in the RSC and ACA were significantly more active during PS than during aWK and SWS, respectively. In addition, neuronal discharge of RSC but not of ACA neurons increased just after the peak of hippocampal theta wave. Our results show for the first time that RSC neurons display enhanced spiking in synchrony with theta specifically during PS. We propose that activation of RSC neurons specifically during PS may play a role in the offline consolidation of spatial memories, and in the generation of vivid perceptual scenery during dreaming. SIGNIFICANCE STATEMENT Fifty years ago, Michel Jouvet used the term paradoxical to define REM sleep because of the simultaneous occurrence of a cortical activation similar to waking accompanied by muscle atonia. However, we recently demonstrated using functional neuroanatomy that only a few limbic structures including the retrosplenial cortex (RSC) and anterior cingulate cortex (ACA) are activated during PS. In the present study, we show for the first time that the RSC and ACA contain neurons firing more during PS than in any other state. Further, RSC neurons are firing in phase with the hippocampal theta rhythm. These data indicate that the RSC is very active during PS and could play a key role in memory consolidation taking place during this state.
Spatiotopic Adaptation in Visual Areas

The ability to perceive the visual world around us as spatially stable despite frequent eye movements is one of the long-standing mysteries of neuroscience. The existence of neural mechanisms processing spatiotopic information is indispensable for a successful interaction with the external world. However, how the brain handles spatiotopic information remains a matter of debate. We here combined behavioral and fMRI adaptation to investigate the coding of spatiotopic information in the human brain. Subjects were adapted by a prolonged presentation of a tilted grating. Thereafter, they performed a saccade followed by the brief presentation of a probe. This procedure allowed dissociating adaptation aftereffects at retinal and spatiotopic positions. We found significant behavioral and functional adaptation in both retinal and spatiotopic positions, indicating information transfer into a spatiotopic coordinate system. The brain regions involved were located in ventral visual areas V3, V4, and VO. Our findings suggest that spatiotopic representations involved in maintaining visual stability are constructed by dynamically remapping visual feature information between retinotopic regions within early visual areas. SIGNIFICANCE STATEMENT Why do we perceive the visual world as stable, although we constantly perform saccadic eye movements? We investigated how the visual system codes object locations in spatiotopic (i.e., external world) coordinates. We combined visual adaptation, in which the prolonged exposure to a specific visual feature alters perception, with fMRI adaptation, where the repeated presentation of a stimulus leads to a reduction in the BOLD amplitude. Functionally, adaptation was found in visual areas representing the retinal location of an adaptor but also at representations corresponding to its spatiotopic position. The results suggest that an active dynamic shift transports information in visual cortex to counteract the retinal displacement associated with saccade eye movements.
Combinatorial library discovery of small molecule inhibitors of lung cancer proliferation and parathyroid hormone-related protein expression

PTHrP (parathyroid hormone-related protein) is abnormally expressed in a substantial majority of lung cancers, especially non-small cell lung cancers, and plays a key role in tumor progression. Thus, this oncoprotein could be a target for treating patients with lung cancer. This study screened combinatorial libraries of heterocyclic amines for inhibitory effects on PTHrP expression and cell proliferation. Two libraries of over 780,000 bis-cyclic thiourea and guanidine compounds each were tested in BEN lung carcinoma cells. The number of PTHrP inhibitors and the magnitude of the reduction in PTHrP were greater for thioureas. Selected lead thiourea compounds decreased cell PTHrP protein content in dose-dependent fashion, reduced relative abundance of PTHrP mRNA, decreased transcripts derived from the PTHrP P3 promoter and reduced activity of a full length PTHrP promoter luciferase construct. Similar effects on PTHrP mRNA were observed in A549 and H441 lung adenocarcinoma cells and in H727 lung carcinoid cells. However, the compounds only inhibited PTHrP protein levels in BEN cells and H727 cells. The compounds reduced the rate of cell proliferation in BEN cells and H727 cells, but not in lines that showed no inhibition of PTHrP protein. These results suggest that cyclic thiourea compounds inhibit PTHrP expression mediated by the P3 promoter, which is widely used in the majority of PTHrP-expressing cells, and that they may inhibit growth of lung cancer cells through the same mechanism. Further work will be necessary to investigate their mechanism for effects on growth of PTHrP-positive tumors in vivo.
Prognostic value of high thymidine kinase activity in patients with previously untreated diffuse large B-cell lymphoma treated by rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone

Abstract The purpose of this study was to investigate prognostic factors for overall survival (OS) among patients with previously untreated diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP). We evaluated four biological parameters, including thymidine kinase (TK) activity. This study included 183 patients. The median level of TK was 14.0 IU/L, which we chose as the cut-off. After a median follow-up time of 50.0 months, the OS rate at 4 years in the high and low TK arm were 46.7% and 66.7%, respectively (p = 0.001). By multivariate analysis, OS was significantly inferior in the high TK arm (hazard ratio 2.705; p = 0.045). The complete response (CR) rate in the high TK arm was significantly worse than in the low TK arm. OS was significantly better in patients who had achieved CR than in those with partial response or less. In conclusion, high TK activity was a strong predictor for short OS and poor response among patients with previously untreated DLBCL treated with R-CHOP.
Autophosphorylated CaMKII Facilitates Spike Propagation in Rat Optic Nerve

Repeated spike firing can transmit information at synapses and modulate spike timing, shape, and conduction velocity. These latter effects have been found to result from voltage-induced changes in ion currents and could alter the signals carried by axons. Here, we test whether Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates spike propagation in adult rat optic nerve. We find that small-, medium-, and large-diameter axons bind anti-Thr286-phosphorylated CaMKII (pT286) antibodies and that, in isolated optic nerves, electrical stimulation reduces pT286 levels, spike propagation is hastened by CaMKII autophosphorylation and slowed by CaMKII dephosphorylation, single and multiple spikes slow propagation of subsequently activated spikes, and more frequent stimulation produces greater slowing. Likewise, exposing freely moving animals to flickering illumination reduces pT286 levels in optic nerves and electrically eliciting spikes in vivo in either the optic nerve or optic chiasm slows subsequent spike propagation in the optic nerve. By increasing the time that elapses between successive spikes as they propagate, pT286 dephosphorylation and activity-induced spike slowing reduce the frequency of propagated spikes below the frequency at which they were elicited and would thus limit the frequency at which axons synaptically drive target neurons. Consistent with this, the ability of retinal ganglion cells to drive at least some lateral geniculate neurons has been found to increase when presented with light flashes at low and moderate temporal frequencies but less so at high frequencies. Activity-induced decreases in spike frequency may also reduce the energy required to maintain normal intracellular Na+ and Ca2+ levels. SIGNIFICANCE STATEMENT By propagating along axons at constant velocities, spikes could drive synapses as frequently as they are initiated. However, the onset of spiking has been found to alter the conduction velocity of subsequent (“follower”) spikes in various preparations. Here, we find that spikes reduce spike frequency in rat optic nerve by slowing follower spike propagation and that electrically stimulated spiking ex vivo and spike-generating flickering illumination in vivo produce net decreases in axonal Ca2+/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation. Consistent with these effects, propagation speed increases and decreases, respectively, with CaMKII autophosphorylation and dephosphorylation. Lowering spike frequency by CaMKII dephosphorylation is a novel consequence of axonal spiking and light adaptation that could decrease synaptic gain as stimulus frequency increases and may also reduce energy use.
Drug driving from a user's perspective

The bulk of research into drug driving in Australia has been undertaken from a road safety orientation where drug driving is viewed within the broader context of road safety and driver behaviour. Such a specific focus precludes the broader behavioural, contextual and cultural issues associated with substance use. This study aimed to address this issue by focusing on drug driving behaviour within the context of illicit substance use. A series of focused interviews were conducted with 211 illicit drug users from urban and regional centres. A consistent theme identified in the interviews was that drug driving was not necessarily viewed as risky behaviour but rather as an outcome of illicit substance use. Further, some interviewees saw their drug use as enhancing their driving skills and frequently the motor vehicle was viewed as a safe place to use. Overall there was agreement among interviewees that the likelihood of being apprehended for drug driving by police was minimal; this perception was reinforced by past experience. The lack of concern for detection of drug driving behaviour suggests that research should continue into the development and implementation of enforcement programs and roadside detection.
Training Working Memory in Childhood Enhances Coupling between Frontoparietal Control Network and Task-Related Regions

Working memory is a capacity upon which many everyday tasks depend and which constrains a child's educational progress. We show that a child's working memory can be significantly enhanced by intensive computer-based training, relative to a placebo control intervention, in terms of both standardized assessments of working memory and performance on a working memory task performed in a magnetoencephalography scanner. Neurophysiologically, we identified significantly increased cross-frequency phase amplitude coupling in children who completed training. Following training, the coupling between the upper alpha rhythm (at 16 Hz), recorded in superior frontal and parietal cortex, became significantly coupled with high gamma activity (at ∼90 Hz) in inferior temporal cortex. This altered neural network activity associated with cognitive skill enhancement is consistent with a framework in which slower cortical rhythms enable the dynamic regulation of higher-frequency oscillatory activity related to task-related cognitive processes. SIGNIFICANCE STATEMENT Whether we can enhance cognitive abilities through intensive training is one of the most controversial topics of cognitive psychology in recent years. This is particularly controversial in childhood, where aspects of cognition, such as working memory, are closely related to school success and are implicated in numerous developmental disorders. We provide the first neurophysiological account of how working memory training may enhance ability in childhood, using a brain recording technique called magnetoencephalography. We borrowed an analysis approach previously used with intracranial recordings in adults, or more typically in other animal models, called “phase amplitude coupling. ”
‘I'd kill anyone who tried to take my band away’: Obesity Surgery, Critical Fat Politics and the ‘problem’ of Patient Demand

Obesity surgery is commonly figured within Fat Studies as the violent mutilation of the fat body, and as the unjustifiable apotheosis of the war on obesity. However, while calls to stop obesity surgery are politically appealing, they are unable to account for positive accounts of surgery, or the rising demand for it, outside of narratives of victimhood or false consciousness. This paper asks how a critical perspective can account for those surgery patients who, regardless of any problems that they or others may have encountered in the process, remain positive advocates for surgery. Drawing on interviews with obesity surgery patients and observations in an obesity surgery clinic, this paper argues that obesity surgery is usefully conceptualised not simply as acquiescence to the anti-fat imperative, or its brutal implementation, but as a complex interaction of interests, desire and power relations which is inseparable from deeply problematic anti-obesity ideologies, but which is not confined to them. I conc.