l-citrulline prevents asymmetric dimethylarginine-mediated reductions in nitric oxide and nitrosative stress in primary human airway epithelial cells.

BACKGROUND: Asthma is associated with reduced systemic levels of l-arginine and increased asymmetric dimethylarginine (ADMA). This imbalance leads to nitric oxide synthase (NOS) uncoupling with reduced nitric oxide (NO) formation and greater oxidative and nitrosative stress. Whether this imbalance also occurs in bronchial epitheliumof asthmatics is unknown. OBJECTIVES: We used primary human bronchial epithelial cells (HBECs) from asthmatics and healthy controls to evaluate: (i) ADMA-mediated NOS uncoupling reduces epithelial production of NO and increases oxygen and nitrogen reactive species, and (ii) l-citrulline can reverse this mechanism by recoupling NOS, restoring NO production and reducing oxidative and nitrosative stress. RESULTS: In HBECsIL-13 and INFγ stimulated NOS2 and increased NOx levels. The addition of ADMA reduced NOx and increased H2 O2 levels (p<0.001). Treatment with l-citrulline (800, 1600 µm) rescued NOx when the l-arginine media concentration was 25 µm but failed to do so with higher concentrations (100 µm). Under reduced l-arginine media conditions, HBECs treated with l-citrulline increased the levels of argininosuccinate, an enzyme that metabolizes l-citrulline to l-arginine. l-citrulline prevented the ADMA-mediated increase in nitrotyrosine in HBECs in cells from asthmatics and controls. CONCLUSIONS AND CLINICAL RELEVANCE: Increasing ADMA reduces NO formation and increases oxidative and nitrosative stress in airway epithelial cells. l-citrulline supplementation restores NO formation, while preventing nitrosative stress. These results, suggest that l-citrulline supplementation may indeed be a powerful approach to restore airway NO production and may have a therapeutic potential in diseases in which there is a defective production of NO.

Microdissection TESE is superior to conventional TESE in patients with nonobstructive azoospermia caused by Y chromosome microdeletions.

Nonobstructive azoospermia is caused in up to 10% by microdeletions of the Y chromosome in the azoospermia factor (AZF) region, which is divided into three nonoverlapping areas (AZFa, AZFb and AZFc). In 25 male patients with AZF microdeletions, the results of two different techniques for surgical sperm retrieval (SR), conventional multilocular TESE and microdissection TESE, were studied retrospectively over a period of 19 years. Conventional multilocular TESE was carried out in 11 patients and microdissection TESE in 14 patients. Successful SR was possible only in patients with isolated AZFc microdeletions, so only the 20 patients with AZFc microdeletions alone were taken into account for the comparison of the both operative techniques. The sperm detection rate for conventional multilocular TESE was 25%, the sperm detection for microdissection TESE was significantly higher with 67%. In all patients, a histological examination of the testicular tissue was carried out, which showed a mixed picture, but Sertoli-cell-only syndrome in most cases. FSH was no prognostic marker for successful SR. In two of six couples performing an intracytoplasmic sperm injection until now, a pregnancy occurred.

Prasugrel plus bivalirudin vs. clopidogrel plus heparin in patients with ST-segment elevation myocardial infarction.

AIMS: Whether prasugrel plus bivalirudin is a superior strategy to unfractionated heparin plus clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has never been assessed in specifically designed randomized trials. METHODS AND RESULTS: The Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 study is an investigator-initiated, randomized, open-label, multicentre trial, designed to test the hypothesis that in STEMI patients with planned primary PCI a strategy based on prasugrel plus bivalirudin is superior to a strategy based on clopidogrel plus heparin in terms of net clinical outcome. Owing to slow recruitment, the trial was stopped prematurely after enrolment of 548 of 1240 planned patients. At 30 days, the primary composite endpoint of death, myocardial infarction, unplanned revascularization of the infarct related artery, stent thrombosis, stroke, or bleeding was observed in 42 patients (15.6%) randomized to prasugrel plus bivalirudin and 40 patients (14.5%) randomized to clopidogrel plus heparin [relative risk, 1.09; one-sided 97.5% confidence interval (CI) 0-1.79, P = 0.680]. The composite ischaemic endpoint of death, myocardial infarction, unplanned revascularization of the infarct-related artery, stent thrombosis, or stroke occurred in 13 patients (4.8%) in the prasugrel plus bivalirudin group and 15 patients (5.5%) in the clopidogrel plus heparin group (relative risk, 0.89; 95% CI 0.40-1.96, P = 0.894). Bleeding according to the HORIZONS-AMI definition was observed in 38 patients (14.1%) in the prasugrel plus bivalirudin group and 33 patients (12.0%) in the clopidogrel plus heparin group (relative risk, 1.18; 95% CI 0.74-1.88, P = 0.543). Results were consistent across various subgroups of patients. CONCLUSION: In this randomized trial of STEMI patients, we were unable to demonstrate significant differences in net clinical outcome between prasugrel plus bivalirudin and clopidogrel plus heparin. Neither the composite of ischaemic complications nor bleeding were favourably affected by prasugrel plus bivalirudin compared with a regimen of clopidogrel plus unfractionated heparin. However, the results must be interpreted in view of the premature termination of the trial. CLINICAL TRIAL REGISTRATION INFORMATION: Unique identifier NCT00976092 (www.clinicaltrials.gov).

Rationale and design of The Intracoronary Stenting and Antithrombotic Regimen-Testing of a six-week versus a six-month clopidogrel treatment Regimen In Patients with concomitant aspirin and oraL anticoagulant therapy following drug-Eluting stenting (ISAR-TRIPLE) study.

BACKGROUND: An increasing number of patients undergoing coronary stenting need lifelong anticoagulation and therefore require a triple therapy typically consisting of aspirin, clopidogrel, and a vitamin K antagonist. Triple therapy confers an elevated bleeding risk as compared with dual therapy; however, omission of either antiplatelet or anticoagulation therapy might increase the risk of stent thrombosis or thrombembolic events. Although guidelines recommend a duration of dual antiplatelet therapy of 6 to 12months after drug-eluting stent (DES) implantation, the optimal duration of dual antiplatelet therapy in patients receiving oral anticoagulation is not known. HYPOTHESIS: We postulate that 6-week clopidogrel therapy after DES implantation as compared with 6-month therapy is associated with improved clinical outcomes in patients undergoing DES implantation receiving concomitant aspirin and vitamin K antagonists. STUDY DESIGN: The ISAR-TRIPLE is a randomized, open-label trial that examines the restriction of clopidogrel therapy from 6 months to 6 weeks after DES implantation in the setting of concomitant aspirin and oral anticoagulant. Patients are randomized in a 1:1 fashion to either 6-week or 6-month clopidogrel therapy. The primary end point is a composite of death, myocardial infarction, definite stent thrombosis, stroke, or major bleeding. The secondary end point comprises ischemic and bleeding complications. According to sample size calculations, a total of 600 patients are required to be enrolled. Clinical follow-up is scheduled at 6 weeks and at 6 and 9 months after randomization. SUMMARY: There is clinical equipoise regarding the optimal duration of triple therapy after DES implantation in patients who need vitamin K antagonist therapy. The ISAR-TRIPLE trial aims to test the hypothesis that a 6-week triple therapy compared with a 6-month triple therapy improves net clinical outcomes.

Echocardiographic measurements of cardiac dimensions correlate better with body length than with body weight or body surface area.

Looking after children means caring for very small infants up to adult-sized adolescents, with weights ranging from 500 g to more than 100 kg and heights ranging from 25 to more than 200 cm. The available echocardiographic reference data were drawn from a small sample, which did not include preterm infants. Most authors have used body weight or body surface area to predict left ventricular dimensions. The current authors had the impression that body length would be a better surrogate parameter than body weight or body surface area. They analyzed their echocardiographic database retrospectively. The analysis included all available echocardiographic data from 6 June 2001 to 15 December 2011 from their echocardiographic database. The authors included 12,086 of 26,325 subjects documented as patients with normal hearts in their analysis by the examining the pediatric cardiologist. For their analysis, they selected body weight, length, age, and aortic and pulmonary valve diameter in two-dimensional echocardiography and left ventricular dimension in M-mode. They found good correlation between echocardiographic dimensions and body surface area, body weight, and body length. The analysis showed a complex relationship between echocardiographic measurements and body weight and body surface area, whereas body length showed a linear relationship. This makes prediction of echo parameters more reliable. According to this retrospective analysis, body length is a better parameter for evaluating echocardiographic measurements than body weight or body surface area and should therefore be used in daily practice.

Characteristics and special challenges of neonatal emergency transports.

BACKGROUND: As a rule, newborns do not require special medical care. If unexpected complications occur peripartum or postpartum, support from and transport to specialised neonatal hospitals might be needed. METHODS: In a retrospective study, all transport protocols of a supraregional paediatric­neonatological maximum care hospital in northwestern Germany from 01.10.2018 through 30.09.2021 were analysed. The particular focus was on transports of newborns (<7 days) and the leading symptoms that led to contact. RESULTS: A total of 299 patients were included (average age of 15.4 h, 61.6 % males). The average complete transport time was approximately 2 h. Five leading neonatal diseases (respiratory, infectious, asphyxia, cardiac, haematological) were found to represent the causes of >80 % of transfers. Respiratory adaptation disorders are the main reason for transferring a newborn to a centre, whereas asphyxia is the most severe condition. The various symptoms differ in their time of onset, a factor which must be taken into account in practice. Differences were also found between different types of hospitals: while a large proportion of transports were carried out from maternity hospitals (80.6 %), children transported from children's hospitals were generally more severely ill. DISCUSSION: Transfers of neonates, especially from maternity hospitals to neonatal intensive care units due to special neonatal diseases, are not rare. In times of increasingly scarce resources, the effective care of sick or at-risk neonates is essential. For low-population regions, this means professional cooperation between maximum care providers and smaller children's hospitals and maternity-only hospitals.

High host-plant nitrogen content: a prerequisite for the evolution of ant-caterpillar mutualism?

The amount of nitrogen required to complete an insect's life cycle may vary greatly among species that have evolved distinct life history traits. Myrmecophilous caterpillars in the Lycaenidae family produce nitrogen-rich exudates from their dorsal glands to attract ants for protection, and this phenomenon has been postulated to shape the caterpillar's host-plant choice. Accordingly, it was postulated that evolution towards myrmecophily in Lycaenidae is correlated with the utilization of nitrogen-rich host plants. Although our results were consistent with the evolutionary shifts towards high-nutrient host plants serving as exaptation for the evolution of myrmecophily in lycaenids, the selection of nitrogen-rich host plants was not confined to lycaenids. Butterfly species in the nonmyrmecophilous family Pieridae also preferred nitrogen-rich host plants. Thus, we conclude that nitrogen is an overall important component in the caterpillar diet, independent of the level of myrmecophily, as nitrogen can enhance the overall insect fitness and survival. However, when nitrogen can be obtained through alternative means, as in socially parasitic lycaenid species feeding on ant brood, the selective pressure for maintaining the use of nutrient-rich host plants is relaxed, enabling the colonization of nitrogen-poor host plants.

Examples of model-free implant restorations using Cerec inLab 4.0 software.

This case report demonstrates two ways to fabricate model-free implant restorations with the Cerec inLab 4.0 software. Because the patient, a woman with a history of periodontal disease, did not wish to have a removable partial denture, implant therapy was planned for the restoration of her edentulous areas 14/15 and 24/25. In addition, the restoration was to provide functional relief of the natural maxillary anterior teeth. The two implants for the first quadrant were planned as single-tooth restorations. Each was designed as a full contour implant supra-structure using the Cerec Biogeneric abutment design technique. After completing the design phase, each restoration proposal was split into two parts: a zirconia abutment and a lithium disilicate crown. For the restoration of the second quadrant, custom 20-degree-angled abutments were individualized and acquired with the Cerec camera. A block crown was then designed, milled in burn-out acrylic resin, and fabricated from a lithium disilicate glass-ceramic ingot according to the press ceramic technique. Additionally methods of provisional restorations are discussed.

When laughter arrests speech: fMRI-based evidence.

Who has not experienced that sensation of losing the power of speech owing to an involuntary bout of laughter? An investigation of this phenomenon affords an insight into the neuronal processes that underlie laughter. In our functional magnetic resonance imaging study, participants were made to laugh by tickling in a first condition; in a second one they were requested to produce vocal utterances under the provocation of laughter by tickling. This investigation reveals increased neuronal activity in the sensorimotor cortex, the anterior cingulate gyrus, the insula, the nucleus accumbens, the hypothalamus and the periaqueductal grey for both conditions, thereby replicating the results of previous studies on ticklish laughter. However, further analysis indicates the activity in the emotion-associated regions to be lower when tickling is accompanied by voluntary vocalization. Here, a typical pattern of activation is identified, including the primary sensory cortex, a ventral area of the anterior insula and the ventral tegmental field, to which belongs to the nucleus ambiguus, namely, the common effector organ for voluntary and involuntary vocalizations. During the conflictual voluntary-vocalization versus laughter experience, the laughter-triggering network appears to rely heavily on a sensory and a deep interoceptive analysis, as well as on motor effectors in the brainstem. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.

Temporal patterns of diversification in Andean Eois, a species-rich clade of moths (Lepidoptera, Geometridae).

The timing of the origin of present day Neotropical animal diversity is still a matter of debate. For a long time, a preponderance of glacial (i.e. Pleistocene) radiations has been proposed. However, recent data from molecular clock studies indicate a preglacial origin for most of the examined taxa. We performed a fossil-calibrated molecular dating analysis of the genus Eois, which is a major component of one of the world's most diverse assemblages of herbivorous insects. We found that diversification of Eois took place in the Miocene following a pattern best explained by density-dependent diversification. A strong slowdown of diversification towards the present was detected. Diversification of Eois does overlap with increased Andean uplift and diversification of the most commonly used host plant genus Piper. These findings match the patterns found for the majority of Neotropical tetrapods and for three other unrelated, ecologically different lepidopteran genera.

Annexin XIIIb: a novel epithelial specific annexin is implicated in vesicular traffic to the apical plasma membrane.

The sorting of apical and basolateral proteins into vesicular carriers takes place in the trans-Golgi network (TGN) in MDCK cells. We have previously analyzed the protein composition of immunoisolated apical and basolateral transport vesicles and have now identified a component that is highly enriched in apical vesicles. Isolation of the encoding cDNA revealed that this protein, annexin XIIIb, is a new isoform of the epithelial specific annexin XIII sub-family which includes the previously described intestine-specific annexin (annexin XIIIa; Wice, B. M., and J. I. Gordon. 1992. J. Cell Biol. 116:405-422). Annexin XIIIb differs from annexin XIIIa in that it contains a unique insert of 41 amino acids in the NH2 terminus and is exclusively expressed in dog intestine and kidney. Immunofluorescence microscopy demonstrated that annexin XIIIb was localized to the apical plasma membrane and underlying punctate structures. Since annexins have been suggested to play a role in membrane-membrane interactions in exocytosis and endocytosis, we investigated whether annexin XIIIb is involved in delivery to the apical cell surface. To this aim we used permeabilized MDCK cells and a cytosol-dependent in vitro transport assay. Antibodies specific for annexin XIIIb significantly inhibited the transport of influenza virus hemagglutinin from the TGN to the apical plasma membrane while the transport of vesicular stomatitis virus glycoprotein to the basolateral cell surface was unaffected. We propose that annexin XIIIb plays a role in vesicular transport to the apical plasma membrane in MDCK cells.

A major transmembrane protein of Golgi-derived COPI-coated vesicles involved in coatomer binding.

Formation of non-clathrin-coated vesicles requires the recruitment of several cytosolic factors to the Golgi membrane. To identify membrane proteins involved in this budding process, a highly abundant type I transmembrane protein (p23) was isolated from mammalian Golgi-derived COPI-coated vesicles, and its cDNA was cloned and sequenced. It belongs to the p24 family of proteins involved in the budding of transport vesicles (Stamnes, M.A., M.W. Craighead, M.H. Hoe, N. Lampen, S. Geromanos, P. Tempst, and J.E. Rothman. 1995. Proc. Natl. Acad. Sci. USA. 92:8011-8015). p23 consists of a large NH2-terminal luminal domain and a short COOH-terminal cytoplasmic tail (-LRRFFKAKKLIE-CO2-) that shows similarity, but not identity, with the sequence motif-KKXX-CO2-, known as a signal for retrieval of escaped ER-resident membrane proteins (Jackson, M.R., T. Nilsson, and P.A. Peterson. 1990. EMBO (Eur. Mol. Biol. Organ.) J. 9:3153-3162; Nilsson, T., M. Jackson, and P.A. Peterson. 1989. Cell. 58:707-718). The cytoplasmic tail of p23 binds to coatomer with similar efficiency as known KKXX motifs. However, the p23 tail differs from the KKXX motif in having an additional motif needed for binding of coatomer. p23 is localized to Golgi cisternae and, during vesicle formation, it concentrates into COPI-coated buds and vesicles. Biochemical analysis revealed that p23 is enriched in vesicles by a factor of approximately 20, as compared with the donor Golgi fraction, and is present in amounts stoichiometric to the small GTP-binding protein ADP-ribosylation factor (ARF) and coatomer. From these data we conclude that p23 represents a Golgi-specific receptor for coatomer involved in the formation of COPI-coated vesicles.

Bimodal interaction of coatomer with the p24 family of putative cargo receptors.

Cytoplasmic domains of members of the p24 family of putative cargo receptors were shown to bind to coatomer, the coat protein of COPI-coated transport vesicles. Domains that contained dilysine endoplasmic reticulum retrieval signals bound the alpha-, beta'-, and epsilon-COP subunits of coatomer, whereas other p24 domains bound the beta-, gamma-, and zeta-COP subunits and required a phenylalanine-containing motif. Transit of a CD8-p24 chimera from the endoplasmic reticulum through the Golgi complex was slowed when the phenylalanine motif was mutated, suggesting that this motif may function as an anterograde transport signal. The either-or bimodal binding of coatomer to p24 tails suggests models for how coatomer can potentially package retrograde-directed and anterograde-directed cargo into distinct COPI-coated vesicles.

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes.

Ant predation on herbivores through a multitrophic lens: how effects of ants on plant herbivore defense and natural enemies vary along temperature gradients.

Ants are keystone predators in terrestrial trophic cascades. Addressing ants' roles in multitrophic interactions across regional gradients is important for understanding mechanisms behind range limits of species. We present four hypotheses of trophic dynamics occurring when ants are rare: first, there is a shift in predator communities; second, plants decrease investments in ant attraction and increase production of secondary metabolites; third, lower herbivory at high elevations allows plants to tolerate herbivory; and fourth, distribution of ant-plants can be limited based on ant abundance. Conducting experiments on multitrophic effects of ants across elevational gradients, and incorporating these results to ecological niche modeling (ENM) will improve our knowledge of the impacts of global change on ants, trophic interactions, and biodiversity.

Impact of bivalirudin on post-procedural epicardial blood flow, risk of stent thrombosis and mortality after percutaneous coronary intervention.

AIMS: We aimed to assess the association of bivalirudin with post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow, acute (≤24 hours) and 30-day stent thrombosis (ST), and one-year mortality. METHODS AND RESULTS: The study included 11,623 patients undergoing percutaneous coronary intervention (PCI). The primary outcomes were post-procedural TIMI flow grade ≤2 and definite acute ST. In groups treated with bivalirudin (n=3,135), abciximab plus unfractionated heparin (UFH; n=3,539) and UFH alone (n=4,949), post-procedural TIMI was ≤2 in 5.2%, 3.2% and 3.2% of patients, respectively (adjusted odds ratio [OR]=1.96 [95% confidence interval] 1.47-2.56 for bivalirudin versus abciximab plus UFH and OR=1.56 [1.20-2.04] for bivalirudin versus UFH). Definite acute ST occurred in two patients (0.06%) treated with bivalirudin, two patients (0.06%) treated with abciximab plus UFH, and seven patients (0.14%) treated with UFH (p=0.47). Bivalirudin was not associated with increased risk of 30-day ST (hazard ratio [HR]=1.20 [0.59-2.43] versus abciximab plus UHF, and HR=0.93 [0.48-1.82] versus UFH) or one-year mortality (HR=0.95 [0.70-1.28] versus abciximab plus UHF, and HR=1.05 [0.78-1.41] versus UFH). CONCLUSIONS: Bivalirudin was associated with higher risk of suboptimal post-PCI TIMI flow but not with increased risk of acute or 30-day definite ST or one-year mortality compared with abciximab plus UFH or UFH alone.

Molecular genetic evidence for subtypes of oligoastrocytomas.

The histogenesis of oligoastrocytomas remains controversial, with some data arguing similarity of oligoastrocytomas to astrocytic tumors, and other data suggesting closer relationships with oligodendroglial neoplasms. Since the molecular genetic changes in astrocytomas differ from those of oligodendrogliomas, we characterized 120 astrocytic and oligodendroglial tumors, including 38 oligoastrocytomas, for genetic alterations that occur disproportionately between astrocytomas and oligodendrogliomas, i.e. TP53 gene mutations and allelic loss of chromosomes 1p, 17p and 19q. As previously reported, TP53 mutations were common in astrocytic gliomas, occurring in approximately half of WHO grade II and III astrocytomas, but in only 5% of WHO grades II and III oligodendrogliomas. Allelic losses of chromosomes 1p and 19q, however, were common in oligodendrogliomas (41% and 63%), but less frequent in astrocytomas (9% and 35%). Oligoastrocytomas showed TP53 mutations in 12/38 (32%) cases and allelic losses of chromosomes 1p and 19q in 52% and 70%, respectively. Most importantly, TP53 mutations and allelic losses on chromosomes 1p and 19q were inversely correlated in oligoastrocytomas (p < 0.011 and p < 0.019). These data suggest the existence of two genetic subsets of oligoastrocytomas, one genetically related to astrocytomas and the other genetically related to oligodendrogliomas. Histologically, those oligoastrocytomas with TP53 mutations were more often astrocytoma-predominant, while those with chromosome 19q loss were more often oligodendroglioma-predominant.

VIP17/MAL, a proteolipid in apical transport vesicles.

VIP17 is a proteolipid enriched in the CHAPS-insoluble complexes from MDCK cells, and a candidate component of the molecular machinery responsible for the sorting and targeting of proteins to the apical surface. Cloning and sequencing of the cDNA encoding the protein revealed that it is the canine homolog of the human and rat MAL proteins. Analysis by immunofluorescence microscopy of epitope-tagged VIP17/MAL expressed transiently in BHK cells and stably in MDCK cells revealed a perinuclear, vesicular, and plasmalemmal staining. In MDCK cells the distribution was mainly in vesicular structures in the apical cytoplasm. These and other results suggest that VIP17/MAL is an important component in vesicular trafficking cycling between the Golgi complex and the apical plasma membrane.

Prohibitin, an antiproliferative protein, is localized to mitochondria.

Prohibitin is a ubiquitously expressed protein with antiproliferative properties. When rat prohibitin tagged with a carboxy-terminal c-Myc epitope was expressed in baby hamster kidney cells the protein was targeted to mitochondria. In immunofluorescence microscopy prohibitin colocalized with a mitochondrial marker E3. Immunoelectron microscopy revealed that prohibitin was associated with the periphery of mitochondria. The amino-terminus of prohibitin shares characteristics of the known mitochondrial import signals, and positioning of the tag at the N-terminus causes accumulation of the protein in the cytoplasm. These findings help to direct functional studies on prohibitin and suggest that a mitochondrial protein may act as a tumor suppressor.

Beware of samples! A cognitive-ecological sampling approach to judgment biases.

A cognitive-ecological approach to judgment biases is presented and substantiated by recent empirical evidence. Latent properties of the environment are not amenable to direct assessment but have to be inferred from empirical samples that provide the interface between cognition and the environment. The sampling process may draw on the external world or on internal memories. For systematic reasons (proximity, salience, and focus of attention), the resulting samples tend to be biased (selective, skewed, or conditional on information search strategies). Because people lack the metacognitive ability to understand and control for sampling constraints (predictor sampling, criterion sampling, selective-outcome sampling, etc.), the sampling biases carry over to subsequent judgments. Within this framework, alternative accounts are offered for a number of judgment biases, such as base-rate neglect, confirmation bias, illusory correlation, pseudo-contingency, Simpson's paradox, outgroup devaluation, and pragmatic-confusion effects.