Locomotor activity differences between sympatric patas monkeys (Erythrocebus patas) and vervet monkeys (Cercopithecus aethiops): Implications for the evolution of long hindlimb length in Homo

Homo erectus is notable for its taller stature and longer lower limbs relative to earlier hominids, but the selective pressures favoring such long limbs are unclear. Among anthropoid primates, patas monkeys (Erythrocebus patas) and extant hominids share several extreme characteristics involved with foraging and movement, including the relatively longest lower limb proportions, longest daily travel distances and largest home ranges for their body or group size, occupancy of some of the driest habitats, and very efficient thermoregulatory systems. We suggest that patas monkeys are an appropriate behavioral model with which to speculate on the selective pressures that might have operated on H. erectus to increase lower limb length. Here, in a comparison of the locomotor activities of patas monkeys and sympatric, closely related vervet monkeys (Cercopithecus aethiops), we provide evidence for the hypothesis that patas use their long stride more to increase foraging efficiency while walking than to run, either from predators or otherwise. Am J Phys Anthropol 105:199–207, 1998. © 1998 Wiley-Liss, Inc.     

Identification of Phytoplankton from Flow Cytometry Data by Using Radial Basis Function Neural Networks

We describe here the application of a type of artificial neural network, the Gaussian radial basis function (RBF) network, in the identification of a large number of phytoplankton strains from their 11-dimensional flow cytometric characteristics measured by the European Optical Plankton Analyser instrument. The effect of network parameters on optimization is examined. Optimized RBF networks recognized 34 species of marine and freshwater phytoplankton with 91.5% success overall. The relative importance of each measured parameter in discriminating these data and the behavior of RBF networks in response to data from “novel” species (species not present in the training data) were analyzed.     

BPIFB1 (LPLUNC1) is upregulated in cystic fibrosis lung disease

Although the biology the PLUNC (recently renamed BPI fold, BPIF) family of secreted proteins is poorly understood, multiple array based studies have suggested that some are differentially expressed in lung diseases. We have examined the expression of BPIFB1 (LPLUNC1), the prototypic two-domain containing family member, in lungs from CF patients and in mouse models of CF lung disease. BPIFB1 was localized in CF lung samples along with BPIFA1, MUC5AC, CD68 and NE and directly compared to histologically normal lung tissues and that of bacterial pneumonia. We generated novel antibodies to mouse BPIF proteins to conduct similar studies on ENaC transgenic (ENaC-Tg) mice, a model for CF-like lung disease. Small airways in CF demonstrated marked epithelial staining of BPIFB1 in goblet cells but staining was absent from alveolar regions. BPIFA1 and BPIFB1 were not co-localised in the diseased lungs. In ENaC-Tg mice there was strong staining of both proteins in the airways and luminal contents. This was most marked for BPIFB1 and was noted within 2?weeks of birth. The two proteins were present in distinct cells within epithelium. BPIFB1 was readily detected in BAL from ENaC-Tg mice but was absent from wild-type mice. Alterations in the expression of BPIF proteins is associated with CF lung disease in humans and mice. It is unclear if this elevation of protein production, which results from phenotypic alteration of the cells within the diseased epithelium, plays a role in the pathogenesis of the disease.     

Phylogenetic and evolutionary analysis of the PLUNC gene family

The PLUNC family of human proteins are candidate host defense proteins expressed in the upper airways. The family subdivides into short (SPLUNC) and long (LPLUNC) proteins, which contain domains predicted to be structurally similar to one or both of the domains of bactericidal/permeability-increasing protein (BPI), respectively. In this article we use analysis of the human, mouse, and rat genomes and other sequence data to examine the relationships between the PLUNC family proteins from humans and other species, and between these proteins and members of the BPI family. We show that PLUNC family clusters exist in the mouse and rat, with the most significant diversification in the locus occurring for the short PLUNC family proteins. Clear orthologous relationships are established for the majority of the proteins, and ambiguities are identified. Completion of the prediction of the LPLUNC4 proteins reveals that these proteins contain approximately a 150-residue insertion encoded by an additional exon. This insertion, which is predicted to be largely unstructured, replaces the structure homologous to the 40s hairpin of BPI. We show that the exon encoding this region is anomalously variable in size across the LPLUNC proteins, suggesting that this region is key to functional specificity. We further show that the mouse and human PLUNC family orthologs are evolving rapidly, which supports the hypothesis that these proteins are involved in host defense. Intriguingly, this rapid evolution between the human and mouse sequences is replaced by intense purifying selection in a large portion of the N-terminal domain of LPLUNC4. Our data provide a basis for future functional studies of this novel protein family.     

A NIMA-related kinase, Fa2p, localizes to a novel site in the proximal cilia of Chlamydomonas and mouse kidney cells

Polycystic kidney disease and related syndromes involve dysregulation of cell proliferation in conjunction with ciliary defects. The relationship between cilia and cell cycle is enigmatic, but it may involve regulation by the NIMA-family of kinases (Neks). We previously showed that the Nek Fa2p is important for ciliary function and cell cycle in Chlamydomonas. We now show that Fa2p localizes to an important regulatory site at the proximal end of cilia in both Chlamydomonas and a mouse kidney cell line. Fa2p also is associated with the proximal end of centrioles. Its localization is dynamic during the cell cycle, following a similar pattern in both cell types. The cell cycle function of Fa2p is kinase independent, whereas its ciliary function is kinase dependent. Mice with mutations in Nek1 or Nek8 have cystic kidneys; therefore, our discovery that a member of this phylogenetic group of Nek proteins is localized to the same sites in Chlamydomonas and kidney epithelial cells suggests that Neks play conserved roles in the coordination of cilia and cell cycle progression.     

Mortality in people with schizophrenia: a systematic review and meta‐analysis of relative risk and aggravating or attenuating factors

People with schizophrenia die 15‐20 years prematurely. Understanding mortality risk and aggravating/attenuating factors is essential to reduce this gap. We conducted a systematic review and random‐effects meta‐analysis of prospective and retrospective, nationwide and targeted cohort studies assessing mortality risk in people with schizophrenia versus the general population or groups matched for physical comorbidities or groups with different psychiatric disorders, also assessing moderators. Primary outcome was all‐cause mortality risk ratio (RR); key secondary outcomes were mortality due to suicide and natural causes. Other secondary outcomes included any other specific‐cause mortality. Publication bias, subgroup and meta‐regression analyses, and quality assessment (Newcastle‐Ottawa Scale) were conducted. Across 135 studies spanning from 1957 to 2021 (schizophrenia: N=4,536,447; general population controls: N=1,115,600,059; other psychiatric illness controls: N=3,827,955), all‐cause mortality was increased in people with schizophrenia versus any non‐schizophrenia control group (RR=2.52, 95% CI: 2.38‐2.68, n=79), with the largest risk in first‐episode (RR=7.43, 95% CI: 4.02‐13.75, n=2) and incident (i.e., earlier‐phase) schizophrenia (RR=3.52, 95% CI: 3.09‐4.00, n=7) versus the general population. Specific‐cause mortality was highest for suicide or injury‐poisoning or undetermined non‐natural cause (RR=9.76‐8.42), followed by pneumonia among natural causes (RR=7.00, 95% CI: 6.79‐7.23), decreasing through infectious or endocrine or respiratory or urogenital or diabetes causes (RR=3 to 4), to alcohol or gastrointestinal or renal or nervous system or cardio‐cerebrovascular or all natural causes (RR=2 to 3), and liver or cerebrovascular, or breast or colon or pancreas or any cancer causes (RR=1.33 to 1.96). All‐cause mortality increased slightly but significantly with median study year (beta=0.0009, 95% CI: 0.001‐0.02, p=0.02). Individuals with schizophrenia <40 years of age had increased all‐cause and suicide‐related mortality compared to those ≥40 years old, and a higher percentage of females increased suicide‐related mortality risk in incident schizophrenia samples. All‐cause mortality was higher in incident than prevalent schizophrenia (RR=3.52 vs. 2.86, p=0.009). Comorbid substance use disorder increased all‐cause mortality (RR=1.62, 95% CI: 1.47‐1.80, n=3). Antipsychotics were protective against all‐cause mortality versus no antipsychotic use (RR=0.71, 95% CI: 0.59‐0.84, n=11), with largest effects for second‐generation long‐acting injectable anti­psychotics (SGA‐LAIs) (RR=0.39, 95% CI: 0.27‐0.56, n=3), clozapine (RR=0.43, 95% CI: 0.34‐0.55, n=3), any LAI (RR=0.47, 95% CI: 0.39‐0.58, n=2), and any SGA (RR=0.53, 95% CI: 0.44‐0.63, n=4). Antipsychotics were also protective against natural cause‐related mortality, yet first‐generation antipsychotics (FGAs) were associated with increased mortality due to suicide and natural cause in incident schizophrenia. Higher study quality and number of variables used to adjust the analyses moderated larger natural‐cause mortality risk, and more recent study year moderated larger protective effects of antipsychotics. These results indicate that the excess mortality in schizophrenia is associated with several modifiable factors. Targeting comorbid substance abuse, long‐term maintenance antipsychotic treatment and appropriate/earlier use of SGA‐LAIs and clozapine could reduce this mortality gap.     

Detection of Iss and Bor on the surface of Escherichia coli

AIMS: To confirm the presence of Iss and Bor on the outer membrane of Escherichia coli using Western blots of outer membrane protein (OMP) preparations and fluorescence microscopy, and explore the use of fluorescence microscopy for the detection of avian pathogenic E. coli (APEC) and diagnosis of avian colibacillosis. METHODS AND RESULTS: Knockout mutants of iss and bor were created using a one-step recombination of target genes with PCR-generated antibiotic resistance cassettes. Anti-Iss monoclonal antibodies (Mabs) that cross-react with Bor protein were used to study the mutants relative to the wild-type organism. These Mabs were used as reagents to study OMP preparations of the mutants with Western blotting and intact E. coli cells with fluorescence microscopy. Iss and Bor were detected in Western blots of OMP preparations of the wild type. Also, Iss was detected on Deltabor mutants, and Bor was detected on Deltaiss mutants. Iss and Bor were also detected on the surface of the intact, wild-type cells and mutants using fluorescence microscopy. CONCLUSIONS: These results demonstrate that Bor and Iss are exposed on E. coli's outer membrane where they may be recognized by the host's immune system. SIGNIFICANCE AND IMPACT OF THE STUDY: To our knowledge, this is the first report confirming Iss' location in the outer membrane of an E. coli isolate. Such surface exposure has implications for the use of these Mabs for APEC detection and colibacillosis control.