Sumoylation silences the plasma membrane leak K+ channel K2P1.

Reversible, covalent modification with small ubiquitin-related modifier proteins (SUMOs) is known to mediate nuclear import/export and activity of transcription factors. Here, the SUMO pathway is shown to operate at the plasma membrane to control ion channel function. SUMO-conjugating enzyme is seen to be resident in plasma membrane, to assemble with K2P1, and to modify K2P1 lysine 274. K2P1 had not previously shown function despite mRNA expression in heart, brain, and kidney and sequence features like other two-P loop K+ leak (K2P) pores that control activity of excitable cells. Removal of the peptide adduct by SUMO protease reveals K2P1 to be a K+-selective, pH-sensitive, openly rectifying channel regulated by reversible peptide linkage

Genetic diversity at the FMR1 locus in the Indonesian population

We report an analysis of allelic diversity at short tandem repeat polymorphisms within the fragile XA locus in 1069 male volunteers from twelve Indonesian sub-populations. An odd numbered allele of DXS548 was found at high frequency in all Indonesian populations. Greater allelic diversity was identified at the loci under study than has been previously reported for an Asian population. These differences distinguish the Indonesian population from all previously reported Asian, European and African populations. A high frequency of small premutation alleles, 4/120 (3.3%, 95% CI 0.9–8.3%), was identified in the Moluccan population of Hiri Island

Assessment of ice mélange impacts on tidewater glacier dynamics using high resolution ICEYE imagery

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Early childhood lung function is a stronger predictor of adolescent lung function in cystic fibrosis than early Pseudomonas aeruginosa infection

Pseudomonas aeruginosa has been suggested as a major determinant of poor pulmonary outcomes in cystic fibrosis (CF), although other factors play a role. Our objective was to investigate the association of early childhood Pseudomonas infection on differences in lung function in adolescence with CF

Effects of experimental design and its role in interpretation of results

A total of 256 weanling pigs (PIC TR4 × 1050, initially 13.8 lb and 21 d of age) were used in a 28-d growth trial to compare allotment methods of a completely randomized design (CRD) and a randomized complete block design (RCBD). Two treatments were used to compare these designs: a negative control with no antibiotic or growth promoter and a positive control with 35 g/ton of Denagard (Novartis Animal Health), 400 g/ton of chlortetracycline, and zinc from zinc oxide at 3,000 and 2,000 ppm in Phases 1 and 2, respectively. Experimental diets were fed in 2 phases: Phase 1 from d 0 to 14 and Phase 2 from d 14 to 28. Eight replications of each dietary treatment were used for each experimental design. The first statistical model examined dietary treatment, experimental design, and the design × dietary treatment as fixed factors. With the exception of pens in the CRD having a trend for improved (P 0.11) for any responses variables, indicating that treatment means reacted similarly in each of the experimental designs. In both the CRD and the RCBD, pig weights were increased (P < 0.003) with supplementation of growth promoters on d 14 and 28. Variation of weight within pen remained the same in the CRD from d 0 to 28 at approximately 20% but increased from 3% on d 0 to 10% on d 28 for the RCBD. Dietary addition of growth promoters increased (P < 0.003) ADG and ADFI and improved F/G (P < 0.04) in both the CRD and RCBD from d 0 to 14, with lower P-values for the CRD than the RCBD. From d 14 to 28, the CRD detected an increase (P < 0.001) in ADG and ADFI with dietary addition of growth promoters, and the RCBD detected an increase (P < 0.001) only in ADFI. Over the entire 28-d trial, growth promoters increased (P < 0.001) ADG and ADFI and improved (P < 0.03) F/G in the CRD and increased (P < 0.02) ADG and ADFI in the RCBD. Lower standard errors for the difference were also estimated for ADG and F/G in the CRD than in the RCBD from d 0 to 28. The average corrected relative efficiency for each of the three periods was 2.08 for ADG, 5.05 for ADFI, and 0.80 for F/G. The gain and intake values suggest that the added variation explained by blocks in the RCBD was beneficial for achieving a more reduced estimate of σ2error compared with analyzing that particular data set as a CRD. The variance ratios of the CRD to RCBD from d 0 to 28 depict the different responses well with ADG at 0.67, ADFI at 1.70, and F/G at 0.22. When these ratios were compared with an F-test, they were well below the upper critical limit of 4.60, suggesting that the CRD offered estimates for σ2error similar to those of the RCBD. With the same estimate for σ2error, the non-centrality parameter for each design would be similar, and therefore, the increase in degrees of freedom (DF) for the error term would lead to greater power to detect differences in the CRD. Additional studies are needed to verify these results and determine whether blocking is an efficient use of error DF

GALA: an international multicentre randomised trial comparing general anaesthesia versus local anaesthesia for carotid surgery

Background: Patients who have severe narrowing at or near the origin of the internal carotid artery as a result of atherosclerosis have a high risk of ischaemic stroke ipsilateral to the arterial lesion. Previous trials have shown that carotid endarterectomy improves long-term outcomes, particularly when performed soon after a prior transient ischaemic attack or mild ischaemic stroke. However, complications may occur during or soon after surgery, the most serious of which is stroke, which can be fatal. It has been suggested that performing the operation under local anaesthesia, rather than general anaesthesia, may be safer. Therefore, a prospective, randomised trial of local versus general anaesthesia for carotid endarterectomy was proposed to determine whether type of anaesthesia influences peri-operative morbidity and mortality, quality of life and longer term outcome in terms of stroke-free survival. Methods/design: A two-arm, parallel group, multicentre randomised controlled trial with a recruitment target of 5000 patients. For entry into the study, in the opinion of the responsible clinician, the patient requiring an endarterectomy must be suitable for either local or general anaesthesia, and have no clear indication for either type. All patients with symptomatic or asymptomatic internal carotid stenosis for whom open surgery is advised are eligible. There is no upper age limit. Exclusion criteria are: no informed consent; definite preference for local or general anaesthetic by the clinician or patient; patient unlikely to be able to co-operate with awake testing during local anaesthesia; patient requiring simultaneous bilateral carotid endarterectomy; carotid endarterectomy combined with another operation such as coronary bypass surgery; and, the patient has been randomised into the trial previously. Patients are randomised to local or general anaesthesia by the central trial office. The primary outcome is the proportion of patients alive, stroke free ( including retinal infarction) and without myocardial infarction 30 days post-surgery. Secondary outcomes include the proportion of patients alive and stroke free at one year; health related quality of life at 30 days; surgical adverse events, re-operation and re-admission rates; the relative cost of the two methods of anaesthesia; length of stay and intensive and high dependency bed occupancy

Primary Ciliary Dyskinesia. Recent Advances in Diagnostics, Genetics, and Characterization of Clinical Disease

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia that leads to oto-sino-pulmonary diseases and organ laterality defects in approximately 50% of cases. The estimated incidence of PCD is approximately 1 per 15,000 births, but the prevalence of PCD is difficult to determine, primarily because of limitations in diagnostic methods that focus on testing ciliary ultrastructure and function. Diagnostic capabilities have recently benefitted from (1) documentation of low nasal nitric oxide production in PCD and (2) discovery of biallelic mutations in multiple PCD-causing genes. The use of these complementary diagnostic approaches shows that at least 30% of patients with PCD have normal ciliary ultrastructure. More accurate identification of patients with PCD has also allowed definition of a strong clinical phenotype, which includes neonatal respiratory distress in >80% of cases, daily nasal congestion and wet cough starting soon after birth, and early development of recurrent/chronic middle-ear and sinus disease. Recent studies, using advanced imaging and pulmonary physiologic assessments, clearly demonstrate early onset of lung disease in PCD, with abnormal air flow mechanics by age 6–8 years that is similar to cystic fibrosis, and age-dependent onset of bronchiectasis. The treatment of PCD is not standardized, and there are no validated PCD-specific therapies. Most patients with PCD receive suboptimal management, which should include airway clearance, regular surveillance of pulmonary function and respiratory microbiology, and use of antibiotics targeted to pathogens. The PCD Foundation is developing a network of clinical centers, which should improve diagnosis and management of PCD

Adaptation to Different Human Populations by HIV-1 Revealed by Codon-Based Analyses

Several codon-based methods are available for detecting adaptive evolution in protein-coding sequences, but to date none specifically identify sites that are selected differentially in two populations, although such comparisons between populations have been historically useful in identifying the action of natural selection. We have developed two fixed effects maximum likelihood methods: one for identifying codon positions showing selection patterns that persist in a population and another for detecting whether selection is operating differentially on individual codons of a gene sampled from two different populations. Applying these methods to two HIV populations infecting genetically distinct human hosts, we have found that few of the positively selected amino acid sites persist in the population; the other changes are detected only at the tips of the phylogenetic tree and appear deleterious in the long term. Additionally, we have identified seven amino acid sites in protease and reverse transcriptase that are selected differentially in the two samples, demonstrating specific population-level adaptation of HIV to human populations

Changes in bird assemblages because of vegetation homogenisation in communal livestock systems

Protected areas are intended to promote biodiversity representation and persistence; yet, whether they are effective in degraded landscapes where much of the original vegetation structure remains intact has received relatively little attention. We test whether avian assemblages in communal rangelands in savannas differ from savannas supporting a full complement of native herbivores and predators. Birds were surveyed in 36 transect counts conducted over 18 days. We also compare the vegetation structure between the two land-use types to assess whether differences in bird assemblages could be attributed to changes in vegetation structure. Bird assemblages were richer, had greater abundances and different compositions inside protected areas than rangelands. The median body mass of birds was larger inside than outside protected areas, and rangelands supported fewer grassland specialists, but more closed-canopy specialists. However, no differences in feeding guild composition were found between protected areas and communal rangelands. Additionally, vegetation structure, but not richness, differed between protected areas and communal rangelands: communal rangelands had higher densities of woody vegetation and shorter grass height than the protected areas. Our findings suggest that the altered vegetation structure in communal grazing camps has led to changes in the species richness and composition of bird communities and has been selected by closed-canopy specialists at the cost of open grassy specialists. Hunting in communal rangelands is likely to have resulted in the loss of large birds and in reductions in bird abundance in the rangelands. Therefore, land-use management that does not lead to irreversible landscape transformation can nevertheless result in changes in the diversity, composition and functioning of native assemblages. Conservation implications: Savanna landscapes that are degraded, but not transformed, support fewer bird species, fewer open habitat specialists and smaller birds because of vegetation homogenisation.South African National Research Foundationhttps://koedoe.co.zapm2020Plant Production and Soil Scienc