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Metallic materials with unique surface structure have attracted much attention due to their unique physical and chemical properties. However, it is hard to prepare bulk metallic materials with special crystal faces, especially at the nanoscale. Herein, we report an efficient method to adjust the surface structure of a Cu plate which combines ion implantation technology with the oxidation-etching process. The large number of vacancies generated by ion implantation induced the electrochemical oxidation of several atomic layers in depth; after chemical etching, the Cu(100) planes were exposed on the surface of the Cu plate. As a catalyst for acid hydrogen evolution reaction, the Cu plate with (100) planes merely needs 273 mV to deliver a current density of 10 mA/cm 2 because the high-energy (100) surface has moderate hydrogen adsorption and desorption capability. This work provides an appealing strategy to engineer the surface structure of bulk metallic materials and improve their catalytic properties.

Copper is known as a conductive metal but an inert catalyst for the hydrogen evolution reaction due to its inappropriate electronic structure. In this work, an active copper catalyst is prepared with high-energy surfaces by adopting the friction stir welding (FSW) technique. FSW can mix the immiscible Fe and Cu materials homogenously and heat them to a high temperature. Resultantly, α-Fe transforms into γ-Fe, and low-energy γ-Fe (100) and (110) surfaces induce the epitaxial growth of high-energy Cu (110) and (100) planes, respectively. After the removal of γ-Fe by acid etching, the copper electrode exposes high-energy surface and exhibits excellent acidic HER activity, even being superior to Pt foil at high current densities (>66 mA cm -2 ). Density functional theory calculation reveals that the high-energy surface favors the adsorption of hydrogen intermediate, thus accelerating the hydrogen evolution reaction. The epitaxial growth induced by FSW opens a new avenue toward engineering high-performance catalysts. In addition, FSW makes it possible to massively fabricate low-cost catalyst, which is advantageous to industrial application., (© 2022 Wiley-VCH GmbH.)

A self-supported silver electrode was prepared by plasma spraying and used for catalysing the hydrogen evolution reaction. Thanks to the non-equilibrium synthetic conditions, the silver catalyst exposes high-energy (200) crystal planes, which enhance the adsorption of hydrogen and improve the intrinsic catalytic activity. As a result, the silver catalyst delivers an overpotential of 349 mV at 10 mA cm -2 , which was much lower than those of Ag foil (742 mV) and commercial Ag powder (657 mV). This work provides a new idea of preparing active electrocatalysts by traditional processes.

As a metal-free photocatalyst, graphitic carbon nitride (g-CN) shows great potential for photocatalytic water splitting, although its performance is significantly limited by structural defects due to incomplete polymerization. In the present work, we successfully synthesize highly conjugated g-CN nanofoam through an iodide substitution technique. The product possesses a high polymerization degree, low defect density, and large specific surface area; as a result, it achieves a hydrogen evolution rate of 9.06 mmol h -1 g -1 under visible light irradiation, with an apparent quantum efficiency (AQE) of 18.9% at 420 nm. Experimental analysis and theoretical calculations demonstrate that the recombination of photogenerated carriers at C-NH x defects was effectively depressed in the nanofoam, giving rise to the high photocatalytic activity.

The surface of an electrocatalyst undergoes dynamic chemical and structural transformations under electrochemical operating conditions. There is a dynamic exchange of metal cations between the electrocatalyst and electrolyte. Understanding how iron in the electrolyte gets incorporated in the nickel hydroxide electrocatalyst is critical for pinpointing the roles of Fe during water oxidation. Here, we report that iron incorporation and oxygen evolution reaction (OER) are highly coupled, especially at high working potentials. The iron incorporation rate is much higher at OER potentials than that at the OER dormant state (low potentials). At OER potentials, iron incorporation favors electrochemically more reactive edge sites, as visualized by synchrotron X-ray fluorescence microscopy. Using X-ray absorption spectroscopy and density functional theory calculations, we show that Fe incorporation can suppress the oxidation of Ni and enhance the Ni reducibility, leading to improved OER catalytic activity. Our findings provide a holistic approach to understanding and tailoring Fe incorporation dynamics across the electrocatalyst-electrolyte interface, thus controlling catalytic processes.

Engineering high-performance electrocatalysts is of great importance for energy conversion and storage. As an efficient strategy, element doping has long been adopted to improve catalytic activity, however, it has not been clarified how the valence state of dopant affects the catalytic mechanism and properties. Herein, it is reported that the valence state of a doping element plays a crucial role in improving catalytic performance. Specifically, in the case of iridium doped nickel-iron layer double hydroxide (NiFe-LDH), trivalent iridium ions (Ir 3+ ) can boost hydrogen evolution reaction (HER) more efficiently than tetravalent iridium (Ir 4+ ) ions. Ir 3+ -doped NiFe-LDH delivers an ultralow overpotential (19 mV @ 10 mA cm -2 ) for HER, which is superior to Ir 4+ doped NiFe-LDH (44 mV@10 mA cm -2 ) and even commercial Pt/C catalyst (40 mV@ 10 mA cm -2 ), and reaches the highest level ever reported for NiFe-LDH-based catalysts. Theoretical and experimental analyses reveal that Ir 3+ ions donate more electrons to their neighboring O atoms than Ir 4+ ions, which facilitates the water dissociation and hydrogen desorption, eventually boosting HER. The same valence-state effect is found for Ru and Pt dopants in NiFe-LDH, implying that chemical valence state should be considered as a common factor in modulating catalytic performance., (© 2021 Wiley-VCH GmbH.)

Metallic catalysts with nanopores are advantageous on improving both activity and selectivity, while the reason behind that remains unclear all along. In this work, porous Zn nanoparticles (P-Zn) were adopted as a model catalyst to investigate the catalytic behavior of metallic nanopores. In situ X-ray absorption spectroscopy, in situ Fourier transform infrared spectroscopy, and density functional theory (DFT) analyses reveal that the concave surface of nanopores works like a pincer to capture and clamp CO 2 and H 2 O precursors simultaneously, thus lowering the energy barriers of CO 2 electroreduction. Resultantly, the pincer mechanism endows P-Zn with a high Faradic efficiency (98.1 %) towards CO production at the potential of -0.95 V vs. RHE. Moreover, DFT calculation demonstrates that Co and Cu nanopores exhibit the pincer behavior as well, suggesting that this mechanism is universal for metallic nanopores., (© 2020 Wiley-VCH GmbH.)

Developing highly efficient and low-cost photocatalysts for overall water splitting has long been a pursuit for converting solar power into clean hydrogen energy. Herein, we demonstrate that a nonstoichiometric nickel-cobalt double hydroxide can achieve overall water splitting by itself upon solar light irradiation, avoiding the consumption of noble-metal co-catalysts. We employed an intensive laser to ablate a NiCo alloy target immersed in alkaline solution, and produced so-called L-NiCo nanosheets with a nonstoichiometric composition and O 2- /Co 3+ ions exposed on the surface. The nonstoichiometric composition broadens the band gap, while O 2- and Co 3+ ions boost hydrogen and oxygen evolution, respectively. As such, the photocatalyst achieves a H 2 evolution rate of 1.7 μmol h -1 under AM 1.5G sunlight irradiation and an apparent quantum yield (AQE) of 1.38 % at 380 nm., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Water electrolysis in alkaline electrolyte is an attractive way toward clean hydrogen energy via the hydrogen evolution reaction (HER), whereas the sluggish water dissociation impedes the following hydrogen evolution. Noble metal oxides possess promising capability for catalyzing water dissociation and hydrogen evolution; however, they are never utilized for the HER due to the instability under the reductive potential. Here it is shown that compressive strain can stabilize RhO 2 clusters and promote their catalytic activity. To this end, a strawberry-like structure with RhO 2 clusters embedded in the surface layer of Rh nanoparticles is engineered, in which the incompatibility between the oxide cluster and the metal substrate causes intensive compressive strain. As such, RhO 2 clusters remain stable at a reduction potential up to -0.3 V versus reversible hydrogen electrode and present an alkaline HER activity superior to commercial Pt/C., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Andersson lesions (ALs), also known as spondylodiscities, destructive vertebral lesions and spinal pseudarthrosis, usually occur in patients with ankylosing spondylitis (AS). Inflammatory and traumatic causes have been proposed to define this lesion. Different surgical approaches including anterior, posterior, and combined anterior and posterior procedure have been used to address the complications, consisting of mechanical pain, kyphotic deformity, and neurologic deficits. However, the preferred surgical procedure remains controversial. The aim of this study was to illustrate the safety, efficacy, and feasibility of a modified posterior wedge osteotomy for the ALs with kyphotic deformity in AS., Methods: From June 2008 to January 2013, 23 patients (18 males, 5 females) at an average age of 44.8 years (range 25-69 years) were surgically treated for thoracolumbar kyphosis with ALs in AS via a modified posterior wedge osteotomy in our department. All sagittal balance parameters were assessed by standing lateral radiography of the whole spine before surgery and during the follow-up period. Assessment of radiologic fusion at follow-up was based on the Bridwell interbody fusion grading system. Ankylosing spondylitis quality of life (ASQoL) and visual analog scale (VAS) scores were performed to evaluate improvements in daily life function and back pain pre-operatively and post-operatively. Paired t tests were used to compare clinical data change in parametric values before and after surgery and the Mann-Whitney U test was employed for non-parametric comparisons. The radiographic data change was evaluated by repeated measure analysis of variance., Results: The mean operative duration was 205.4 min (range 115-375 min), with an average blood loss of 488.5 mL (range 215-880 mL). Radiographical and clinical outcomes were assessed after a mean of 61.4 months of follow-up. The VAS back pain and ASQoL scores improved significantly in all patients (7.52 ± 1.31 vs. 1.70 ± 0.70, t = 18.30, P < 0.001; 13.87 ± 1.89 vs. 7.22 ± 1.24, t = 18.53, P < 0.001, respectively). The thoracolumbar kyphosis (TLK) changed from 40.03 ± 17.61° pre-operatively to 13.86 ± 6.65° post-operatively, and 28.45 ± 6.63° at final follow-up (F = 57.54, P < 0.001), the thoracic kyphosis (TK) changed from 52.30 ± 17.62° pre-operatively to 27.76 ± 6.50° post-operatively, and 28.45 ± 6.63° at final follow-up (F = 57.29, P < 0.001), and lumbar lordosis (LL) changed from -29.56 ± 9.73° pre-operatively to -20.58 ± 9.71° post-operatively, and -20.73 ± 10.27° at final follow-up (F = 42.50, P < 0.001). Mean sagittal vertical axis (SVA) was improved from 11.82 ± 4.55 cm pre-operatively to 5.12 ± 2.42 cm post-operatively, and 5.03 ± 2.29 cm at final follow-up (F = 79.36, P < 0.001). No obvious loss of correction occurred, according to the lack of significant differences in the sagittal balance parameters between post-operatively and the final follow-up in all patients (TK: 27.76 ± 6.50° vs. 28.45 ± 6.63°, TLK: 13.86 ± 6.65° vs. 14.42 ± 6.7°, LL: -20.58 ± 9.71° vs. -20.73 ± 10.27°, and SVA: 5.12 ± 2.42 cm vs. 5.03 ± 2.29 cm, all P > 0.05, respectively)., Conclusions: The modified posterior wedge osteotomy is an accepted surgical procedure for treating thoracolumbar kyphosis with ALs in AS and results in satisfactory local kyphosis correction, solid fusion, and good clinical outcomes.

Engineering surface structure of catalysts is an efficient way towards high catalytic performance. Here, we report on the synthesis of regular iridium nanospheres (Ir NSs), with abundant atomic steps prepared by a laser ablation technique. Atomic steps, consisting of one-atom level covering the surface of such Ir NSs, were observed by aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) . The prepared Ir NSs exhibited remarkably enhanced activity both for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in acidic medium. As a bifunctional catalyst for overall water splitting, they achieved a cell voltage of 1.535 V @ 10 mA/cm 2 , which is much lower than that of Pt/C-Ir/C couple (1.630 V @ 10 mA/cm 2 ).

Objective: To explore the therapeutic efficacy of manual reduction combined with percutaneous vertebroplasty in treating osteoporotic vertebral compression fractures(OVCFs) with intravertebral clefts., Methods: The clinical data of 94 patients with osteoporotic vertebral compression fractures with intravertebral clefts treated from January 2014 to January 2017 were retrospectively analyzed. The patients were divided into group A and group B according to different operative methods. In group A, 45 patients were treated with unilateral approach PVP, including 17 males and 28 females, aged (75.35±11.82) years old, with a bone density T-value of (-4.28±0.65) g/cm³; in group B, 49 patients treated with manual reduction combined with unilateral approach PVP, including 19 males and 30 females, aged (76.79±9.64) years old, with a bone density T-value of (-4.33±0.72) g/cm³. The operation time, bone cement injection volume and postoperative complications of two groups were recorded. The VAS and ODI scores of two groups were analyzed respectively at 1, 12, 18 months after operation. Vertebral height and kyphosis Cobb angle of two groups were compared immediately after surgery and 12, 18 months after operation. The distribution of bone cement in the vertebral body was observed and its distribution excellent rate was calculated., Results: There was no significant difference in operation time between two groups. The amount of bone cement injection was(8.42±1.24) ml in group A and(9.19±1.09) ml in group B, and the difference between two groups was statistically significant( P <0.05). No spinal nerve root injury during operation and no complications including pulmonary embolism, bone cement toxicity and infection were found in two groups. There were 5 cases of bone cement leakage in group A and 4 cases in group B, which did not cause corresponding clinical symptoms and were not treated additionally. The distribution of bone cement in group A was excellent in 25 cases, good in 19 cases, poor in 1 case and in group B was excellent in 45 cases, good in 4 cases. The distribution excellent rate of bone cement was higher in group B than in group A ( P <0.05). The VAS and ODI scores before operation and 1, 12, 18 months after operation were 8.29±0.74, 2.59±0.14, 3.75±0.38, 3.84±0.88 and 40.04±3.16, 9.24±2.82, 12.27±2.64, 15.83±2.58 in group A, 8.22±0.82, 2.54±0.19, 2.81±0.23, 2.82±0.45 and 39.98±2.05, 9.16±2.10, 9.46±2.41, 9.76±2.46 in group B. There was no significant difference in VAS and ODI scores at 1 month after operation between two groups ( P >0.05), but group A was higher than group B at 12 and 18 months after operation ( P <0.05). The vertebral height and Cobb angle before surgery, immediately after surgery, and 12, 18 months after surgery in group A were(59.17±1.42)%, (85.95±2.19)%, (75.27±3.45)%, (68.34±2.24)% and(23.83±3.37)°, (15.26±2.61)°, (17.63±2.16)°, (19.46±2.54)°, and in group B were(59.31±1.87)%, (89.19±2.53)%, (88.62±2.51)%, (88.59±2.62)% and(24.72±3.78)°, (14.91±2.28)°, (15.48±2.55)°, (15.86±2.81)°. Vertebral height Immediately after surgery was greater in group B than in group A and Cobb angle in group B was smaller than in group A ( P <0.05). During follow-up, there was no significant change in vertebral height in group B, while vertebral body recollapse in group A( P <0.05)., Conclusions: In the treatment of osteoporotic vertebral compression fractures with intravertebral clefts, the manual reduction combined with PVP is more effective than single PVP, which can effectively prevent vertebral body recollapse and improve the long-term efficacy of patients., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

FeCo2O4 nanoparticles with abundant oxygen vacancies were produced by laser fragmentation. The oxygen vacancies can lower the thermodynamic energy barriers as well as accelerate the electron transfer, eventually promoting oxygen evolution and reduction reactions simultaneously.

Introduction of lattice strain into catalysts is a facile way to modify catalytic behaviour. Here, we report the synthesis of Pd nanoparticles with compressive strain by pulsed laser ablation of a Pd target immersed in an aqueous solution. The intensive quenching effect induces obvious compressive strain which improves the ORR performance of the Pd nanoparticles significantly.

Low-cost and high-performance catalysts are of great significance for electrochemical water splitting. Here, it is reported that a laser-synthesized catalyst, porous Co 0.75 Ni 0.25 (OH) 2 nanosheets, is highly active for catalyzing overall water splitting. The porous nanosheets exhibit low overpotentials for hydrogen evolution reaction (95 mV@10 mA cm -2 ) and oxygen evolution reaction (235 mV@10 mA cm -2 ). As both anode and cathode catalysts, the porous nanosheets achieve a current density of 10 mA cm -2 at an external voltage of 1.56 V, which is much lower than that of commercial Ir/C-Pt/C couple (1.62 V). Experimental and theoretical investigations reveal that numerous Co 3+ ions are generated on the pore wall of nanosheets, and the unique atomic structure around Co 3+ ions leads to appropriate electronic structure and adsorption energy of intermediates, thus accelerating hydrogen and oxygen evolution., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A hybrid electrocatalyst CoO/r-NLG with a high density of pyridinic-N-Co bonds was synthesized via pyrolysis treatments of a mixture of cobalt iron precursors and laser-induced mesoporous N-doped graphene, which achieved superb reversible ORR/OER activities, offering a low efficiency loss (ΔE) of 0.635 V in a 1.0 M KOH electrolyte.

Decompression is the major therapeutic strategy for acute spinal cord injury, but there is some debate about the time window for decompression following spinal cord injury. An important goal and challenge in the treatment of spinal cord injury is inhibiting or reversing secondary injury. Governor Vessel electroacupuncture can improve symptoms of spinal cord injury by inhibiting cell apoptosis and improving the microenvironment of the injured spinal cord. In this study, Governor Vessel electroacupuncture combined with decompression at different time points was used to treat acute spinal cord injury. The rat models were established by inserting a balloon catheter into the atlanto-occipital space. The upper cervical spinal cord was compressed for 12 or 48 hours prior to decompression. Electroacupuncture was conducted at the acupoints Dazhui (GV14) and Baihui (GV 20) (2 Hz, 15 minutes) once a day for 14 consecutive days. Compared with decompression alone, hind limb motor function recovery was superior after decompression for 12 and 48 hours combined with electroacupuncture. However, the recovery of motor function was not significantly different at 14 days after treatment in rats receiving decompression for 12 hours. Platelet-activating factor levels and caspase-9 protein expression were significantly reduced in rats receiving electroacupuncture compared with decompression alone. These findings indicate that compared with decompression alone, Governor Vessel electroacupuncture combined with delayed decompression (48 hours) is more effective in the treatment of upper cervical spinal cord injury. Governor Vessel electroacupuncture combined with early decompression (12 hours) can accelerate the recovery of nerve movement in rats with upper cervical spinal cord injury. Nevertheless, further studies are necessary to confirm whether it is possible to obtain additional benefit compared with early decompression alone., Competing Interests: The authors have no conflicts of interest to declare

Objective: To explore the effect and underlying mechanism of decompression(DE)combined with Governor Vessel(GV)electro-acupuncture(EA) on rats with acute severe upper cervical spinal cord compression injury., Methods: Thirty SPF rats were randomly divided into 5 groups(control group A, B and experiment group C, D, E), 6 rats in each group. The model of acute severe upper cervical spinal cord compression injury were made by forcing a balloon catheter put in atlas pillow clearance. The group A was blank one, the group B put balloon catheter in atlas pillow clearance without forcing, and the group C, D, E sustained compressed for 48 h. The group C received electric acupuncture intervention, selecting the Baihui and Dazhui point, having the continuous wave and frequency of 2 Hz, with the treatment time of 15 min and continuous treatment for 14 d; the group D received methylprednisolone intervention, injected by caudal vein; the group E did not received any intervention again. The arterial blood and injured spinal cord tissue of all the rats were obtained after 14 days' treatment, and BBB score was used to evaluate the change of each group hind limbs motor function, the contents of platelet activating factor(PAF) in injured spinal cord tissue and blood serum were assess by ELISA method; the Caspase-9 expression for each group after 14 days' treatment was assess by Western blot method., Results: BBB scores were(21.000±0.000) points at the 6 time points, that was, 1 h, 48 h after forcing in control group, 24 h, 3 d, 7 d, 14 d after treating in experiment group; the score of experimental groups (group C, D, E) were always lower than control groups(group A, B); compared with group E, group C and D were significantly higher( P <0.05); and there was no significant difference between group C and group D( P >0.05). The results of PAF by ELISA method to measure:the concentration of serum PAF, there was no statistical difference among group A, B, D, E ( P >0.05), group C was lower than the other groups ( P <0.05); the concentration of tissue PAF, there was no significant difference between group A and group B( P >0.05), group D was significantly higher than that of group A, B, and C( P <0.05), group E was the highest one than that of the other groups( P <0.05). Western blot med tests showed that the Caspase-9 protein expression in group A and B was similar ( P >0.05), group C was higher than that of group A and B( P <0.05), group D was higher than group A, B and C( P <0.05), group E was the highest than that of group A, B, C and D ( P <0.05)., Conclusions: Decompression and Governor Vessel electro-acupuncture on acute severe upper cervical spinal cord compression injury had a better effect compare with decompression and methylprednisolone or simple decompression only, its mechanism may be related to lower the PAF levels and downregulating Caspase-9 protein expression in spinal injury tissue., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

Cubic Cu(1.4)S nanoparticles were synthesized on a large scale by laser ablation of salt powder dispersed in an organic solvent. A metastable Cu(1.4)S phase was formed at high temperature in a reductive solvent and was maintained at room temperature due to the quenching effect of the pulsed laser. The cubic Cu(1.4)S nanoparticles show good stability after being exposed to ambient atmosphere for as long as 1 month.

Myxococcus xanthus is a member of the Myxococcales order within the Deltaproteobacteria subdivision. The myxobacteria reside in soil, have relatively large genomes, and display complex life cycles. Here, we report the whole-genome shotgun sequence of strain DZ2, which includes unique genes not found previously in strain DK1622.

Here we report the discovery of tetracyclic benzothiazepines (BTZs) as highly potent and selective antimalarials along with the identification of the Plasmodium falciparum cytochrome bc(1) complex as the primary functional target of this novel compound class. Investigation of the structure activity relationship within this previously unexplored chemical scaffold has yielded inhibitors with low nanomolar activity. A combined approach employing genetically modified parasites, biochemical profiling, and resistance selection validated inhibition of cytochrome bc(1) activity, an essential component of the parasite respiratory chain and target of the widely used antimalarial drug atovaquone, as the mode of action of this novel compound class. Resistance to atovaquone is eroding the efficacy of this widely used antimalarial drug. Intriguingly, BTZ-based inhibitors retain activity against atovaquone resistant parasites, suggesting this chemical class may provide an alternative to atovaquone in combination therapy., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Plasmodium falciparum NDH2 (pfNDH2) is a non-proton pumping, rotenone-insensitive alternative enzyme to the multi-subunit NADH:ubiquinone oxidoreductases (Complex I) of many other eukaryotes. Recombinantly expressed pfNDH2 prefers coenzyme CoQ(0) as an acceptor substrate, and can also use the artificial electron acceptors, menadione and dichlorophenol-indophenol (DCIP). Previously characterized NDH2 inhibitors, dibenziodolium chloride (DPI), diphenyliodonium chloride (IDP), and 1-hydroxy-2-dodecyl-4(1H)quinolone (HDQ) do not inhibit pfNDH2 activity. Here, we provide evidence that HDQ likely targets another P. falciparum mitochondrial enzyme, dihydroorotate dehydrogenase (pfDHOD), which is essential for de novo pyrimidine biosynthesis.

Control of gene expression is poorly understood in the Plasmodium system, where relatively few homologues to known eukaryotic transcription factors have been uncovered. Recent evidence suggests that the parasite may utilize a combinatorial mode of gene regulation, with multiple cis-acting sequences contributing to overall activity at individual promoters [1]. To further probe this mechanism of control, we first searched for over-represented sequence motifs among gene clusters sharing similar expression profiles in Plasmodium falciparum. More specifically, we applied bioinformatic tools to a previously characterized micro-array data set from drug-treated asexual stage cultures (Gunasekera et al., submitted). Cluster analysis of 600 drug responsive genes identified only a single 5' motif, GAGAGAA. Two additional 5' motifs, ACTATAAAGA and TGCAC, were also shared among loci displaying patterns of coordinate expression across varying asexual growth stages. Secondly and most importantly, the functional relevance of each motif was tested in two independent assays-transient transfection and gel-retardation experiments. The GAGAGAA and TGCAC motifs were both active in the former. The GAGAGAA and ACTATAAAGA elements formed specific RNA-protein, but not DNA-protein complexes in gel shift assays, suggesting a key level of control at the RNA level. This is the first report of functionally characterized motifs in P. falciparum that were uncovered following clustering analysis of its asexual stage transcriptome. Together, both the bioinformatic and functional data reported here imply that multiple forms of gene regulation, including post-transcriptional control, may be important in the malarial system.

Work from several laboratories over the past decade indicates that the acquisition of constitutive telomerase expression is a critical step during the malignant transformation of human cells. Normal human cells transiently express low levels of telomerase, the ribonucleoprotein responsible for extending and maintaining telomeres, and exhibit telomere shortening after extended passage, whereas most cancers exhibit constitutive telomerase expression and maintain telomeres at stable lengths. These observations establish a direct connection between immortalization and stabilization of telomere structure. However, recent work suggests that telomerase also contributes to cancer development beyond its role in maintaining stable telomere lengths. In this review, we summarize recent observations that support the concept that telomerase plays multiple roles in facilitating human cell transformation.

In Drosophila melanogaster, apoptosis is controlled by the integrated actions of the Grim-Reaper (Grim-Rpr) and Drosophila Inhibitor of Apoptosis (DIAP) proteins (reviewed in refs 1 4). The anti-apoptotic DIAPs bind to caspases and inhibit their proteolytic activities. DIAPs also bind to Grim-Rpr proteins, an interaction that promotes caspase activity and the initiation of apoptosis. Using a genetic modifier screen, we identified four enhancers of grim-reaper-induced apoptosis that all regulate ubiquitination processes: uba-1, skpA, fat facets (faf), and morgue. Strikingly, morgue encodes a unique protein that contains both an F box and a ubiquitin E2 conjugase domain that lacks the active site Cys required for ubiquitin linkage. A reduction of morgue activity suppressed grim-reaper-induced cell death in Drosophila. In cultured cells, Morgue induced apoptosis that was suppressed by DIAP1. Targeted morgue expression downregulated DIAP1 levels in Drosophila tissue, and Morgue and Rpr together downregulated DIAP1 levels in cultured cells. Consistent with potential substrate binding functions in an SCF ubiquitin E3 ligase complex, Morgue exhibited F box-dependent association with SkpA and F box-independent association with DIAP1. Morgue may thus have a key function in apoptosis by targeting DIAP1 for ubiquitination and turnover.