Protein overabundance is driven by growth robustness.

Protein expression levels optimize cell fitness: Too low an expression level of essential proteins will slow growth by compromising essential processes; whereas overexpression slows growth by increasing the metabolic load. This trade-off naïvely predicts that cells maximize their fitness by sufficiency, expressing just enough of each essential protein for function. We test this prediction in the naturally-competent bacterium Acinetobacter baylyi by characterizing the proliferation dynamics of essential-gene knockouts at a single-cell scale (by imaging) as well as at a genome-wide scale (by TFNseq). In these experiments, cells proliferate for multiple generations as target protein levels are diluted from their endogenous levels. This approach facilitates a proteome-scale analysis of protein overabundance. As predicted by the Robustness-Load Trade-Off (RLTO) model, we find that roughly 70% of essential proteins are overabundant and that overabundance increases as the expression level decreases, the signature prediction of the model. These results reveal that robustness plays a fundamental role in determining the expression levels of essential genes and that overabundance is a key mechanism for ensuring robust growth.

Exploring the impacts of high-speed rail on technology-intensive manufacturing: the case of the Yangtze River Delta region, 2007-2016.

High-speed rail (HSR) may influence economic activities that rely heavily on innovation by facilitating skilled labour, face-to-face interactions, and knowledge spillovers. This study explores how HSR development affects the spatial distribution of technology-intensive manufacturing (TIM) in the Yangtze River Delta (YRD), China. Using a panel dataset including 24 cities for the period 2007-2016 and employing the output of communications equipment, computers, and other electronic equipment (CCOE) as a proxy for TIM's economic productivity at the city level, we apply the staggered difference-in-differences (DID) and spatial Durbin model (SDM) to measure the impacts of HSR's initial opening and connectivity on CCOE development and capture the spatial spillover effects of HSR connectivity. Our findings indicate that the initial opening of HSR and HSR connectivity are negatively associated with CCOE productivity in both DID and SDM. Additionally, the reduction of CCOE is more pronounced in cities with larger populations and higher levels of economy. Moreover, HSR has a more significant effect on CCOE than other manufacturing sectors. However, the spillover effects remain insignificant, indicating HSR's limited impact on CCOE development in adjacent cities within the YRD.

Protein overabundance is driven by growth robustness.

Protein expression levels optimize cell fitness: Too low an expression level of essential proteins will slow growth by compromising essential processes; whereas overexpression slows growth by increasing the metabolic load. This trade-off naïvely predicts that cells maximize their fitness by sufficiency, expressing just enough of each essential protein for function. We test this prediction in the naturally-competent bacterium Acinetobacter baylyi by characterizing the proliferation dynamics of essential-gene knockouts at a single-cell scale (by imaging) as well as at a genome-wide scale (by TFNseq). In these experiments, cells proliferate for multiple generations as target protein levels are diluted from their endogenous levels. This approach facilitates a proteome-scale analysis of protein overabundance. As predicted by the Robustness-Load Trade-Off (RLTO) model, we find that roughly 70% of essential proteins are overabundant and that overabundance increases as the expression level decreases, the signature prediction of the model. These results reveal that robustness plays a fundamental role in determining the expression levels of essential genes and that overabundance is a key mechanism for ensuring robust growth.

A cytochrome bd repressed by a MarR family regulator confers resistance to metals, nitric oxide, sulfide, and cyanide in Chromobacterium violaceum.

Chromobacterium violaceum is a ubiquitous environmental pathogen. Despite its remarkable adaptability, little is known about the mechanisms of stress resistance in this bacterium. Here, in a screen for iron-susceptible transposon mutants, we identified a cytochrome bd that protects C. violaceum against multiple stresses. The two subunits of this cytochrome bd (CioAB) are encoded by the cioRAB operon, which also encodes a GbsR-type MarR family transcription factor (CioR). A Δ cioAB mutant strain was sensitive to iron and the iron-requiring antibiotic streptonigrin and showed a decrease in siderophore production. Growth curves and survival assays revealed that the Δ cioAB strain was also sensitive to zinc, hydrogen peroxide, nitric oxide, sulfide, and cyanide. Expression analysis showed that the promoter activity of the cioRAB operon and the transcript levels of the cioAB genes were increased in a Δ cioR mutant. CioR bound the promoter region of the cio operon in vitro , indicating that CioR is a direct repressor of its own operon. Expression of the cio operon increased at high cell density and was dependent on the quorum-sensing regulator CviR. As cyanide is also a signal for cio expression, and production of endogenous cyanide is known to be a quorum sensing-regulated trait in C. violaceum , we suggest that CioAB is a cyanide-insensitive terminal oxidase that allow respiration under cyanogenic growth conditions. Our findings indicate that the cytochrome bd CioAB protects C. violaceum against multiple stress agents that are potentially produced endogenously or during interactions with a host. IMPORTANCE: The terminal oxidases of bacterial respiratory chains rely on heme-copper (heme-copper oxidases) or heme (cytochrome bd ) to catalyze reduction of molecular oxygen to water. Chromobacterium violaceum is a facultative anaerobic bacterium that uses oxygen and other electron acceptors for respiration under conditions of varying oxygen availability. The C. violaceum genome encodes multiple respiratory terminal oxidases, but their role and regulation remain unexplored. Here, we demonstrate that CioAB, the single cytochrome bd from C. violaceum , protects this bacterium against multiple stressors that are inhibitors of heme-copper oxidases, including nitric oxide, sulfide, and cyanide. CioAB also confers C. violaceum resistance to iron, zinc, and hydrogen peroxide. This cytochrome bd is encoded by the cioRAB operon, which is under direct repression by the MarR-type regulator CioR. In addition, the cioRAB operon responds to quorum sensing and to cyanide, suggesting a protective mechanism of increasing CioAB in the setting of high endogenous cyanide production.

How far can air pollution affect tourism in China? Evidence from panel unconditional quantile regressions.

Previous studies provide empirical evidence for the connection between air pollution and tourism. However, many of them take the nexus as a linear one. It remains unexplored whether any thresholds are required for the nexus to materialize. This study systematically investigates whether PM2.5 concentrations-an essential indicator of air pollution-affect tourism in China at various tourism development levels. We analyze 284 Chinese cities from 2008 to 2018 using the Unconditional Quantile Regression method. Our statistical results reveal that air pollution positively influences tourism (regarding tourist visits and tourism revenue) in areas with low tourism development levels. However, a complex correlation between air pollution and tourism emerges when tourism development has reached a certain level. The correlation is initially negative, then positive, and finally disappears. But, the overall correlation remains negative. The effects of the interaction between air pollution and tourism resources on tourism are inverted U-shaped, implying that tourism resources can mitigate the negative effects of air pollution on tourism only when tourism development has reached a certain level. Based on the above findings, the associated policy implications are discussed.

Installation of the developing nephron in the fetal human kidney during advanced pregnancy.

BACKGROUND: The kidneys of preterm and low birth weight babies reflect vulnerability, since several noxae can evoke the termination of nephron formation. This again leads to oligonephropathy with severe consequences for health in the later life. While the clinical parameters have been intensely investigated, only little is known about the initial traces left by the noxae. For the fetal human kidney, solely the lack of basophilic S-shaped bodies and the reduction in width of the nephrogenic zone were registered. It is not known in how far also the involved progenitor cells, the earlier nephron stages, the collecting duct (CD) ampullae, and the local interstitium are collaterally harmed. AIM: The interstitium at the forming nephron is heterogeneously structured. Thereby, it fulfills quite different mastering and integrative tasks. Since data dealing with the installation of a nephron is not available, the microanatomical features were recorded. RESULTS: The microscopic specimens show that the installation of the transient stages of nephron anlage is not synchronized. Instead, it is controlled within a nephrogenic compartment of the nephrogenic zone. It starts near the renal capsule by positioning the nephrogenic niche so that the nephrogenic progenitor cells face the epithelial progenitor cell at the tip of a CD ampulla. Then, the induced nephrogenic progenitor cells assimilate in the pretubular aggregate. While its medial part remains opposite the head of the CD ampulla, at its proximal end, the primitive renal vesicle is formed. Only a part of it separates to stick to the section border between the head and conus of the CD ampulla. This marks the link with the future connecting tubule at the distal pole of the extending renal vesicle. Meanwhile, the proximal pole is mounted next to the connecting tubule of an earlier developed nephron. The resulting two-point mounting serves a common elongation of the conus at the CD ampulla and the medial aspect of the comma-shaped body. In the S-shaped body, it supports to defoliate the arising glomerulus and to link it with the perforating radiate artery at its deep lateral aspect. CONCLUSIONS: The investigation depicts that the installation is an interactive process between the stages of nephron anlage and its structural neighbors. A special meaning has the interjacent interstitium. It is vital for the positioning, shaping, and physiological integration. Due to its special location, this is mainly exposed to noxae.

The interstitium at the developing nephron in the fetal kidney during advanced pregnancy - a microanatomical inventory.

BACKGROUND: A series of noxae can evoke the termination of nephron formation in preterm and low birth weight babies. This results in oligonephropathy with severe consequences for health in the later life. Although the clinical parameters have been extensively investigated, little is known about the initial damage. Previous pathological findings indicate the reduction in width of the nephrogenic zone and the lack of S-shaped bodies. Current morphological investigations suggest that due to the mutual patterning beside the forming nephron, also its structural neighbors, particularly the interjacent interstitium, must be affected. However, beside the findings on integrative and mastering functions, systematic microanatomical data explaining the configuration of the interstitium at the developing nephron in the fetal kidney during advanced pregnancy is not available. Therefore, this work explains the typical features. RESULTS: The generated data depicts that the progenitor cells, nephrogenic niche, pretubular aggregate, and mesenchymal-to-epithelial transition are restricted to the subcapsular interstitium. During the proceeding development, only the distal pole of the renal vesicles and comma- and S-shaped bodies stays in further contact with it. The respective proximal pole is positioned opposite the peritubular interstitium at the connecting tubule of an underlying but previously formed nephron. The related medial aspect faces the narrow peritubular interstitium of a collecting duct (CD) ampulla first only at its tip, then at its head, conus, and neck, and finally at the differentiating CD tubule. The lateral aspect starts at the subcapsular interstitium, but then it is positioned along the wide perivascular interstitium of the neighboring ascending perforating radiate artery. When the nephron matures, the interstitial configuration changes again. CONCLUSIONS: The present investigation illustrates that the interstitium at the forming nephron in the fetal kidney consists of existing, transient, stage-specific, and differently far matured compartments. According to the developmental needs, it changes its shape by formation, degradation, fusion, and rebuilding.

The Effect of Neuropriming and Focus of Attention on Amateur Standing Long Jump Performance.

Non-invasive brain stimulation has been prominent in recent neurophysiology research. The use of brain stimulation has not been examined in combination with the focus of attention paradigm, an established motor control tool. Therefore, the purpose of this study was to examine the effects of both brain stimulation and focus of attention on the outcome performance, peak force, lower extremity joint kinematics, and projection angle of a standing long jump. Forty-one participants were assigned to either the brain stimulation group or placebo group via a counterbalance design based on leg length and jump distance. Participants were only accepted if they had not previously trained in the standing long jump. On a second day, participants performed a standing long jump under control, external, and internal attentional foci after having undergone either a single session of brain stimulation or a placebo warm-up. Five total jumps were performed: one baseline jump followed by two for each attentional focus condition. The results indicated that an external focus of attention and control conditions created a reduced projection angle compared to an internal focus of attention and that brain stimulation did not have any effects on the performance of a standing long jump after a single session. There were no changes evident between hip, knee, and ankle joint angles, force production, or jump distance between any of the conditions or groups.

Comprehensive well-being scale: development and validation among Chinese in recovery of mental illness in Hong Kong.

BACKGROUND: Given the absence of a brief scale that reconciles and encompasses different conceptual definitions of well-being (physical, psychological, social and spiritual), the present research aimed at developing and validating a Comprehensive Well-Being Scale (CWBS) that encompasses these different conceptual definition and extend the definition of well-being to transcendental well-being among individuals in recovery of mental illness. The present research focuses on testing the scale among people in recovery of mental illness so that a brief and theoretically comprehensive scale would be available for mental health organization to evaluate the well-being of service users, and to develop and evaluate well-being related services. METHODS: A 56-item preliminary well-being scale was developed by a professional panel. In Study 1, 300 mental health service users in Hong Kong were recruited. Twenty items were selected through principal component analysis to form the CWBS. In Study 2, another sample of 300 service users was recruited. Confirmatory factor analysis was done to confirm a two-factor structure. Validity of the scale was also examined. RESULTS: The CWBS yielded good internal consistency (Cronbach's alphas = .79-.91). The finding supported a two-factor structure, namely Intrapersonal Well-Being, and Transpersonal Well-Being, χ2 (169) = 335.61, p < .001, CFI = .90, RMSEA = .06, SRMR = .06. CONCLUSIONS: The CWBS established concurrent and construct validity in assessing well-being among Chinese in recovery of mental illness in Hong Kong. It provided theoretical and practical implications for measuring well-being. Theoretically, it extended the concept of well-being to encompass transcendental well-being in model of recovery among individuals recovery from mental illness. Practically, it provided a tool for evaluation of well-being and service development in mental health organization.

The mutual patterning between the developing nephron and its covering tissues-valid reasons to rethink the search for traces left by impaired nephrogenesis.

BACKGROUND: The impairment of nephrogenesis can cause the termination of nephron formation in preterm and low birth weight babies. This leads to oligonephropathy with severe health consequences in later life. Although many clinical parameters are known, surprisingly little information is available regarding the initial damage on the developing nephron. Equally astounding, the first morphological data regarding the specifics of nephron formation in the nephrogenic zone of the fetal human kidney during late gestation has only been published within the past few years. In this context, it was observed that each stage of nephron anlage is surrounded by a specific set of tissues. Although highly relevant for the normal progress of nephron formation, the mutual patterning has not been systematically described. RESULTS: To contribute, the different stages of nephron anlage in the nephrogenic zone of the fetal human kidney during late gestation were screened by the optical microscope and documented by images. Following this, magnifications (28 × 18 cm) were produced to trace the contours of the developing nephron and its covering tissues. The resulting sketches, almost true to scale, were scanned, edited, and processed by a design program. As a base, first the individual position, size, and shape of the nephrogenic niche, pretubular aggregate, renal vesicles, comma- and S-shaped bodies are presented. Secondly, their structural relations to the renal capsule, collecting duct ampulla, perforating radiate artery, and expanding interstitium are shown. Third of all, the focus is on less considered configurations, such as site-specific approximation, local distancing, punctual adhesion, integration, separation, delamination, formation of congruent and divergent surfaces, and folding and opening of interstitial clefts. CONCLUSIONS: The present contribution illuminates the mutual patterning between the developing nephron and its covering tissues. It is indispensable to know about the microanatomical relations, in order to identify whether the noxae impairing nephrogenesis targets only the developing nephron or also its covering tissues as interacting and controlling instances.

Effects of Heart Rate Biofeedback, Sleep, and Alertness on Marksmanship Accuracy during a Live-fire Stress Shoot.

On the job, law enforcement may be required to utilize lethal force to maintain personal or public safety. Officers' attention to detail, decision-making, and marksmanship accuracy (MA) may be impaired by reduced sleep, increased heart rate (HR), and breathing rate (BR). HR biofeedback (emWave, EW) may help mitigate these impairments. This study sought to determine the impact EW had on MA, stress shoot time-to-completion (TTC), HR and BR versus placebo (PLA). Ten activeduty police officers volunteered for this study. Officers completed two live-fire stress shoots on a 25-m gun range (i.e., familiarization, followed by EW, or PLA trials). MA was assessed as "hit, no-hit." HR and BR were monitored before, immediately after, and 20 minutes post-trial. Sleep was monitored during the entirety of the study. Dependent t-tests were conducted for MA and TTC. A 2x3 repeated-measures ANOVA was conducted for HR, BR, before, during, and after each trial. There were no statistical differences (EW vs. PLA) for: HR (128 ± 23 vs. 136 ± 14; p = 0.30), BR (19 ± 2 vs. 21 ± 2; p = 0.31), TTC (108.4 ± 11.2s vs. 111.6 ± 20.2s; p = 0.94; d = 0.21). Alertness (83.2 ± 9.5 vs. 77.9 ± 15.5), was not statistically significant EW vs. PLA (p = 0.32; d = 0.42). MA (81.4 ± 10.2 vs. 85.9 ± 12.9%) was not statistically significant EW vs. PLA (p = 0.95; d = 0.38). Sleep (7.4 ± 2.9h vs. 5.4 ± 1.7h) was not statistically significant EW vs. PLA (p = 0.13; d = 1.0). EW usage did not affect the physiological and marksmanship performance of officers during a live-fire stress shoot based on HR, BR, TTC, and MA while considering sleep quantity.

Microanatomy of the developing nephron in the fetal human kidney during late gestation.

BACKGROUND: Clinical experiences reveal that the kidneys of preterm and low birth weight infants are highly vulnerable. Noxae of various molecular composition can damage the outer renal cortex, resulting in an early termination of nephron formation. However, in contrast to what is known about the rodent kidney, with reference to the damage on the early stages of nephron anlage such as the comma-shaped body, renal vesicles, pretubular aggregate or nephrogenic niche, this information in the fetal human kidney is not available. The few documented pathological alterations in the fetal human kidney during late gestation are glomeruli with a dilated Bowman's space and a shrunken tuft, the reduction in width of the nephrogenic zone and the lack of here contained S-shaped bodies. The latter points out that the shaping, folding or expansion of the developing nephron must be disrupted. Since these specific aspects have been little investigated, the aim of the present microanatomical contribution is to highlight it. METHODS: Firstly, the individual stages of nephron anlage in the fetal human kidney during late gestation were documented by microscopic images. Then, as a stylistic tool for the pointing to specific sites of the running developmental process, a series of true to scale sketches were produced. RESULTS: The generated sketches depict the spatial expansion of the transiently appearing stages of nephron anlage. These are restricted to the nephrogenic zone and are framed by the inner side of the renal capsule, the related collecting duct ampulla and a perforating radiate artery. Practical hints and a consequent nomenclature explain the developmental course and help us to identify the precise location of the proximal - distal poles, medial - lateral profiles, connecting points, adhesion sites or folds at the developing nephron on microscopic specimens. CONCLUSIONS: The impairment of nephrogenesis in preterm and low birth weight babies is an unsolved biomedical issue. To contribute, by provided true to scale sketches, numerous practical hints and a consequent nomenclature typical features of nephron formation in the fetal human kidney at late gestation are demonstrated.

Shaping of the nephron - a complex, vulnerable, and poorly explored backdrop for noxae impairing nephrogenesis in the fetal human kidney.

BACKGROUND: The impairment of nephrogenesis is caused by noxae, all of which are significantly different in molecular composition. These can cause an early termination of nephron development in preterm and low birth weight babies resulting in oligonephropathy. For the fetal human kidney, there was no negative effect reported on the early stages of nephron anlage such as the niche, pretubular aggregate, renal vesicle, or comma-shaped body. In contrast, pathological alterations were identified on subsequently developing S-shaped bodies and glomeruli. While the atypical glomeruli were closely analyzed, the S-shaped bodies and the pre-stages received little attention even though passing the process of nephron shaping. Since micrographs and an explanation about this substantial developmental period were missing, the shaping of the nephron in the fetal human kidney during the phase of late gestation was recorded from a microanatomical point of view. RESULTS: The nephron shaping starts with the primitive renal vesicle, which is still part of the pretubular aggregate at this point. Then, during extension of the renal vesicle, a complex separation is observed. The medial part of its distal pole is fixed on the collecting duct ampulla, while the lateral part remains connected with the pretubular aggregate via a progenitor cell strand. A final separation occurs, when the extended renal vesicle develops into the comma-shaped body. Henceforth, internal epithelial folding generates the tubule and glomerulus anlagen. Arising clefts at the medial and lateral aspect indicate an asymmetrical expansion of the S-shaped body. This leads to development of the glomerulus at the proximal pole, whereas in the center and at the distal pole, it results in elongation of the tubule segments. CONCLUSIONS: The present investigation deals with the shaping of the nephron in the fetal human kidney. In this important developmental phase, the positioning, orientation, and folding of the nephron occur. The demonstration of previously unknown morphological details supports the search for traces left by the impairment of nephrogenesis, enables to refine the assessment in molecular pathology, and provides input for the design of therapeutic concepts prolonging nephrogenesis.

In Search of Imprints Left by the Impairment of Nephrogenesis.

Clinical aspects dealing with the impairment of nephrogenesis in preterm and low birth weight babies were intensely researched. In this context it was shown that quite different noxae can harm nephron formation, and that the morphological damage in the fetal kidney is rather complex. Some pathological findings show that the impairment leads to changes in developing glomeruli that are restricted to the maturation zone of the outer cortex in the fetal human kidney. Other data show also imprints on the stages of nephron anlage including the niche, the pretubular aggregate, the renal vesicle, and comma- and S-shaped bodies located in the overlying nephrogenic zone of the rodent and human kidneys. During our investigations it was noticed that the stages of nephron anlage in the fetal human kidney during the phase of late gestation have not been described in detail. To contribute, these stages were recorded along with corresponding images. The initial nephron formation in the rodent kidney served as a reference. Finally, the known imprints left by the impairment in both specimens were listed and discussed. In sum, the relatively paucity of data on nephron formation in the fetal human kidney during the late phase of gestation is a call to start with intense research so that concepts for a therapeutic prolongation of nephrogenesis can be designed.

The Evolution of SlyA/RovA Transcription Factors from Repressors to Countersilencers in Enterobacteriaceae.

Gene duplication and subsequent evolutionary divergence have allowed conserved proteins to develop unique roles. The MarR family of transcription factors (TFs) has undergone extensive duplication and diversification in bacteria, where they act as environmentally responsive repressors of genes encoding efflux pumps that confer resistance to xenobiotics, including many antimicrobial agents. We have performed structural, functional, and genetic analyses of representative members of the SlyA/RovA lineage of MarR TFs, which retain some ancestral functions, including repression of their own expression and that of divergently transcribed multidrug efflux pumps, as well as allosteric inhibition by aromatic carboxylate compounds. However, SlyA and RovA have acquired the ability to countersilence horizontally acquired genes, which has greatly facilitated the evolution of Enterobacteriaceae by horizontal gene transfer. SlyA/RovA TFs in different species have independently evolved novel regulatory circuits to provide the enhanced levels of expression required for their new role. Moreover, in contrast to MarR, SlyA is not responsive to copper. These observations demonstrate the ability of TFs to acquire new functions as a result of evolutionary divergence of both cis-regulatory sequences and in trans interactions with modulatory ligands.IMPORTANCE Bacteria primarily evolve via horizontal gene transfer, acquiring new traits such as virulence and antibiotic resistance in single transfer events. However, newly acquired genes must be integrated into existing regulatory networks to allow appropriate expression in new hosts. This is accommodated in part by the opposing mechanisms of xenogeneic silencing and countersilencing. An understanding of these mechanisms is necessary to understand the relationship between gene regulation and bacterial evolution. Here we examine the functional evolution of an important lineage of countersilencers belonging to the ancient MarR family of classical transcriptional repressors. We show that although members of the SlyA lineage retain some ancestral features associated with the MarR family, their cis-regulatory sequences have evolved significantly to support their new function. Understanding the mechanistic requirements for countersilencing is critical to understanding the pathoadaptation of emerging pathogens and also has practical applications in synthetic biology.

Key features of the nephrogenic zone in the fetal human kidney-hardly known but relevant for the detection of first traces impairing nephrogenesis.

In healthy newborn babies, nephrogenesis proceeds unnoticed until birth. With start of the perinatal period, morphogenetic activity in the renal outer cortex consisting of an inner maturation zone and an outer nephrogenic zone is downregulated by unknown signals. One of the results is that the entire nephrogenic zone as well as the contained progenitor cells and niches disintegrate. In contrast, a too early inactivation of the nephrogenic zone takes place in the kidneys of preterm and low birth weight babies. Although they are born in a period of active nephrogenesis, pathological findings show that they evolve to a high incidence oligonephropathy. However, very few data exist about cell biological changes that are evoked by harming, further most of causing molecules, exact cell targets, and related molecular pathways are not identified. Although impairment of nephrogenesis was the subject of research in animal species, there is only limited information available pertaining to the pathological traces in the nephrogenic zone of the human fetal kidney. In this situation, the lack of basic morphological data is particularly aggravating. Surprisingly, there are not even ultrastructural investigations available. Since concrete information is lacking also in relevant textbooks, the current contribution likes to present key features of the nephrogenic zone in the fetal human kidney. Simultaneously, it is a call to explore systematically a hardly known area.

Facile access to deep red/near-infrared emissive AIEgens for efficient non-doped OLEDs.

Notwithstanding the huge demand in bio-imaging and optoelectronics, the construction of highly emissive deep red/near infrared (DR/NIR) organic luminogens is still a big challenge because a narrow energy gap generally leads to low photoluminescence quantum yield. It is even more difficult to afford DR/NIR emitters in the solid state due to the aggregation caused quenching (ACQ) effect. In this work, we found that the direct attachment of a tetraphenylethylene substituted arylamine to the electron accepting 2,1,3-benzothiadiazole produces DR/NIR AIE luminogens with bright emission facilely and efficiently. And the emission wavelengths could be tuned from the red to the DR/NIR region by regulating the variety of the substituents. The long emission wavelength and high photoluminescence quantum yield of these AIEgens are ascribed to the effective intramolecular charge transfer and the suppressed intramolecular motion. Furthermore, non-doped OLEDs based on one of the AIEgens showed an EL emission at 684 nm with a large radiance of 5772 mW Sr-1 m-2 and an impressive external quantum efficiency (EQE) of 1.73%.

Review of radiological screening programmes for breast, lung and pancreatic malignancy.

The premise of medical screening is to identify clinically occult disease, facilitating intervention at an early stage with the intention of improving prognosis. Identifying solid organ malignancy before nodal or distal metastases have occurred unanimously offers the best chance of successful radical treatment, thus there is clearly a potential significant mortality benefit for successful oncological screening programmes. However, the negative consequences of screening have to be considered, particularly the impact of intervening in asymptomatic populations. Diagnostic radiology has an invaluable ability to non-invasively detect disease and has developed an essential role in several oncological screening programmes with new programmes emerging. These include the established mammography screening programme for breast carcinoma, the emerging CT screening programme for lung carcinoma and a new proposed radiological screening programme for pancreatic carcinoma. Results from published randomized controlled trials analysing the benefits of radiological screening have been convoluted and conflicting. Cancer screening remains a widely contested topic and it is a challenge for both radiologist and clinician to assess the risks and benefits at both a population and individual patient level. In this article, we discuss radiological screening and analyse the current literature on these programmes, with evaluation of recently published studies and ongoing trials.

Modulation of H-NS transcriptional silencing by magnesium.

The bacterial histone-like protein H-NS silences AT-rich DNA, binding DNA as 'stiffened' filaments or 'bridged' intrastrand loops. The switch between these modes has been suggested to depend on the concentration of divalent cations, in particular Mg2+, with elevated Mg2+ concentrations associated with a transition to bridging. Here we demonstrate that the observed binding mode is a function of the local concentration of H-NS and its cognate binding sites, as well as the affinity of the interactions between them. Mg2+ does not control a binary switch between these two modes but rather modulates the affinity of this interaction, inhibiting the DNA-binding and silencing activity of H-NS in a continuous linear fashion. The direct relationship between conditions that favor stiffening and transcriptional silencing activity suggests that although both modes can occur in the cell, stiffening is the predominant mode of binding at silenced genes.

PfCap380 as a marker for Plasmodium falciparum oocyst development in vivo and in vitro.

BACKGROUND: Despite the importance of the Plasmodium berghei oocyst capsule protein (PbCap380) in parasite survival, very little is known about the orthologous Plasmodium falciparum capsule protein (PfCap380). The goal of this work was to study the growth of P. falciparum oocysts using PfCap380 as a developmental marker. METHODS: To study P. falciparum oocyst development using both in vivo (mosquito-derived) and in vitro (culture-derived) growth conditions, antibodies (polyclonal antisera) were raised against PfCap380. For studies on in vivo oocysts, mature P. falciparum gametocytes were fed to Anopheles stephensi mosquitoes. For studies on in vitro parasites, P. falciparum gametocytes were induced and matured for subsequent ookinete production. Ookinetes were purified and then tested for binding affinity to basal lamina components and transformation into early oocysts, which were grown on reconstituted basal lamia coated wells with novel oocyst media. To monitor in vivo oocyst development, immunofluorescence assays (IFA) were performed using anti-PfCap380 antisera on Pf-infected mosquito midguts. IFA were also performed on culture-derived oocysts to follow in vitro oocyst development. RESULTS: The anti-PfCap380 antisera allowed detection of early midgut oocysts starting at 2 days after gametocyte infection, while circumsporozoite protein was definitively observed on day 6. For in vitro culture, significant transformation of gametocytes to ookinetes (24%) and of ookinetes to early oocysts (85%) was observed. After screening several basal lamina components, collagen IV provided greatest binding of ookinetes and transformation into early oocysts. Finally, PfCap380 expression was observed on the surface of culture-derived oocysts but not on gametocytes or ookinetes. CONCLUSIONS: This study presents developmental monitoring of P. falciparum oocysts produced in vivo and in vitro. The anti-PfCap380 antisera serves as an important reagent for developmental studies of oocysts from the mosquito midgut and also from oocyst culture using in vitro methodology. The present data demonstrate that PfCap380 is a useful marker to follow the development and maturation of in vivo and in vitro produced oocysts as early as 2 days after zygote formation. Further in vitro studies focused on oocyst and sporozoite maturation will support the manufacturing of whole sporozoites for malaria vaccines.