Griffithsin Retains Anti-HIV-1 Potency with Changes in gp120 Glycosylation and Complements Broadly Neutralizing Antibodies PGT121 and PGT126.

Griffithsin (Grft) is an antiviral lectin that has been shown to potently inhibit HIV-1 by binding high-mannose N-linked glycosylation sites on HIV-1 gp120. A key factor for Grft potency is glycosylation at N295 of gp120, which is directly adjacent to N332, a target glycan for an entire class of broadly neutralizing antibodies (bNAbs). Here, we unify previous work on the importance of other glycans to Grft potency against HIV-1 and Grft's role in mediating the conformational change of gp120 by mutating nearly every glycosylation site in gp120. In addition to a significant loss of Grft activity by the removal of glycosylation at N295, glycan absence at N332 or N448 was found to have moderate effects on Grft potency. Interestingly, in the absence of N295, Grft effectiveness could be improved by a mutation that results in the glycan at N448 shifting to N446, indicating that the importance of individual glycans may be related to their effect on glycosylation density. Grft's ability to alter the structure of gp120, exposing the CD4 binding site, correlated with the presence of glycosylation at N295 only in clade B strains, not clade C strains. We further demonstrate that Grft can rescue the activity of the bNAbs PGT121 and PGT126 in the event of a loss or a shift of glycosylation at N332, where the bNAbs suffer a drastic loss of potency. Despite targeting the same region, Grft in combination with PGT121 and PGT126 produced additive effects. This indicates that Grft could be an important combinational therapeutic

Precision and Recall Reject Curves for Classification

For some classification scenarios, it is desirable to use only those classification instances that a trained model associates with a high certainty. To obtain such high-certainty instances, previous work has proposed accuracy-reject curves. Reject curves allow to evaluate and compare the performance of different certainty measures over a range of thresholds for accepting or rejecting classifications. However, the accuracy may not be the most suited evaluation metric for all applications, and instead precision or recall may be preferable. This is the case, for example, for data with imbalanced class distributions. We therefore propose reject curves that evaluate precision and recall, the recall-reject curve and the precision-reject curve. Using prototype-based classifiers from learning vector quantization, we first validate the proposed curves on artificial benchmark data against the accuracy reject curve as a baseline. We then show on imbalanced benchmarks and medical, real-world data that for these scenarios, the proposed precision- and recall-curves yield more accurate insights into classifier performance than accuracy reject curves.Comment: 11 pages, 3 figures. Updated figure label

Role of the Kinesin-like Protein KipB in Aspergillus nidulans

Molecular motors are protein machines, which power almost all forms of movement in the living world. Among the best known are the motors that hydrolyze ATP and use the derived energy to generate force. They are involved in a variety of diverse cellular functions as vesicle and organelle transport, cytoskeleton dynamics, morphogenesis, polarized growth, cell movements, spindle formation, chromosome movement, nuclear fusion, and signal transduction. Three superfamilies of molecular motors, kinesins, dyneins, and myosins, have so far been well characterized. These motors use microtubules (in the case of kinesines and dyneins) or actin filaments (in the case of myosins) as tracks to transport cargo materials within a cell. Analysis of fungal genomes revealed at least 10 distinct kinesins in filamentous fungi, some of which are not found in yeasts. We used the motor domain of conventional kinesin (KinA) from Aspergillus nidulans to perfom BLAST searches at the public A. nidulans genome database, at the Whitehead Center for Genome Research (Cambridge USA), and identified eleven putative kinesin motors. They grouped into nine of the eleven families, two kinesins being found in the Unc104 familiy and interestingly, one did not fall into any of the known families. The present work analyses the function of a kinesin-like protein in A. nidulans, KipB, which is a member of the Kip3 kinesin family. This family includes one representative in Saccharomyces cerevisiae (Kip3, the family founding member), two in Schizosaccharomyces pombe, Klp5 and Klp6 and one in Drosophila, Klp67A, the single one reported so far for higher eukaryotes in this family. Kip3 kinesins are implicated in microtubule disassembly and are required for chromosome segregation in mitosis and meiosis. To assess the function of KipB kinesin in A. nidulans, a kipB disruption strain was constructed. Analysis of the DkipB mutant revealed new features concerning the cellular functions of Kip3 proteins, but also some conserved ones. kipB is not essential for vegetative growth, and meiosis and ascospore formation were not affected in the DkipB mutant. The KipB protein was shown to be involved in the turnover of interphase cytoplasmic, mitotic and astral microtubules. DkipB mutants are less sensitive to the microtubule-destabilizing drug benomyl, and the microtubule cytoskeleton of interphase cells in DkipB mutants appears altered. Interestingly, spindle morphology and positioning were severely affected. Spindles were highly mobile, could overpass each other, moved over long distances through the cytoplasm, and displayed in 64% of the cases an extremely bent shape, latter feature being the first time reported for Kip3 kinesins. Mitotic progression was delayed in the DkipB mutant and a higher number of cytoplasmic microtubules remained intact during mitosis. DkipB heterozygous strains showed an increased instability of diploid nuclei, which proved once more KipB involvement in mitosis, along with DkipB clear genetic interaction with a mutation in another mitotic kinesin in A. nidulans, bimC4. An N-terminal GFP-KipB construct localized to cytoplasmic microtubules in interphase cells and to spindle and astral microtubules during mitosis, in a discontinuous pattern. Speckles of GFP-KipB appeared to be aligned in the cell. Time-lapse video microscopy indicated that the spots were moving independently towards the microtubule plus ends. This advanced the hypothesis that KipB could display processivity and intrinsic motility along microtubules, or that other kinesins involved in organelle motility are able to target the KipB protein to the microtubule plus ends. In the case of C-terminally truncated GFP-KipB protein versions, a stronger GFP signal was obtained and colocalization with a-tubulin-GFP revealed that they uniformly stain cytoplasmic, mitotic and astral microtubules. This suggests that the C-terminus is important for the correct localization and the movement of KipB protein along microtubules

The underground protest of the café concert

La afirmación ontológica de la identidad supone una lucha discursiva/simbólica (y en ocasiones también física) entre enunciadores de la historia –en este caso, los artistas del café concert, por un lado, y quienes se oponían a dicho proceso de constitución alternativo de identidad, por el otro–. La coerción directa por parte del campo de poder sobre estos espectáculos contestatarios hizo mermar uno de estos términos, dado que la identidad era pensada desde una concepción esencialista/totalizadora y no había cauce para un discurso cuestionador. En los café concert se desarticulaba el concepto de identidad. Esta problematización en el concepto puede analizarse, como bien lo hace Arfuch (2005: 24), en la sustitución de las preguntas “cómo somos” o “de dónde venimos” por el “cómo usamos los recursos del lenguaje, la historia y la cultura en el proceso de devenir más que de ser, cómo nos representamos, somos representados o podríamos representarnos”. La puesta en escena puso en cuestión la representatividad de quienes actuaban en la esfera del poder y deconstruyó su mundo simbólico; la consecuencia fue el pase de la lucha discursiva a la violencia física como intento de supresión de la configuración de una identidad alternativa.The ontological assertion of identity supposes a discursive/ symbolic (and sometimes also physical) struggle between enunciators of history –in this case, the artists of the café concert and those who opposed such process of alternative constitution of identity–. The direct coercion of the agents of power over these challenging spectacles reduced one of these terms, since the identity was thought from an essentialist/ totalizing conception and there was no space for a questioning discourse. In the café-concert, the concept of identity was dismantled. This deconstruction of the concept can be analyzed, as Arfuch (2005: 24) does, considering the substitution of the questions “how are we” or “where do we come from” for the questions “how do we use the resources of language, history and culture in the process of becoming more than being, how do we represent ourselves, how are we represented or how could we represent ourselves in the future”. This stagings questioned the representativeness of those who acted in the sphere of power and deconstructed their symbolic world; the consequence was the passage from the discursive struggle to phy

La teatralidad de/en algunos textos onettianos: el juego con la visibilidad de los procedimientos (muerte, recursividad e incesancia)

Los textos de Juan Carlos Onetti -tanto las novelas como los cuentos del autor uruguayo- desbordan de teatralidad al exhibir lúdicamente el artificio, el proceso de creación, la ficcionalización de su obra. Su trabajo hace visible la puesta en escena de su escritura, que es tratada discursivamente -a modo de guiño- por sus personajes. De esta manera, expone cómo construye sus relatos, pone en evidencia el mecanismo o procedimiento escriturario, lo cuenta, lo narra; ficcionaliza sobre el mismo.Juan Carlos Onetti's texts -both the novels as the stories of the Uruguayan author- overflow of theatricality as they playfully exhibit the artifice, the creation process, the fictionalization of his work. Onetti makes visible the mise en scene of his writing, which is treated -as a wink to the readers- by his prominent figures in their speech. Hereby, he exposes how he constructs his statements, puts in evidence the mechanism or writing procedure, tells it, narrates it; fictionalizes on the same one

Movement patterns and shelter choice of spiny-cheek crayfish (Orconectes limosus) in a large lake’s littoral zone

he study of individual movement patterns and habitat choice is a fundamental step to assess an invasive species’ range extension and to inform possible management options. The spiny-cheek crayfish is an invasive species currently spreading in Europe and also in Lake Constance. This is of concern because the greater Lake Constance area still holds refugial populations of native crayfish that might be endangered by the invader. In invasive crayfish, individual movement patterns and the availability of suitable shelters can predict an invasive population’s spread. In a radio telemetry and mark-recapture study and in semi-natural outdoor experiments, we investigated movement patterns and shelter choice of spiny-cheek crayfish. In the field, radio-tagged and marked crayfish moved distances up to 1200 m within 4 and 13 days, respectively and mostly prevailed within the littoral zone at less than 3 m depth. Tracked crayfish resided close to artificial structures such as boat harbours in the study area. In the outdoor experiments spiny-cheek crayfish used litter as daytime shelter but also chose natural stones and macrophytes. We provide the first large- lake telemetry data on crayfish movement and our results suggest that spiny-cheek crayfish will expand its range within the lake moving along the shoreline. Artificial structures such as boat harbours and litter might facilitate this spread by providing suitable shelters. Our results can help to inform the implementation of countermeasures against the spread of invasive crayfish populations

Breeding biology review of White‑backed Stilt Himantopus melanurus in Brazil and a case study in the largest restinga protected area (Aves, Charadriiformes, Recurvirostridae)

In Brazil, the White-backed Stilt Himantopus melanurus is distributed in the midwest, south and southeast but breeding information is scarce. In this study, species breeding information in the country was compiled from online platform (WikiAves, eBird) and literature. A case study describing nests and egg biometry were reported in Restinga of Jurubatiba National Park (RJNP), on the north cost of Rio de Janeiro state, as well potential threats to the species. Sampling was carried out in September and December 2018, monthly in 2019 and between January to March and September to December in 2020. Overall, 70 breeding records were compiled, between 1997 and November 2021, being 64 from WikiAves in all regions of Brazil, four records from eBird in São Paulo state (in 2021) and two records in literature (one from São Paulo state, in 2007 and one from Rio de Janeiro in 2012). In RJNP, 44 nests were identified being 34 active, with an average of 3.5 eggs per nest, and overall 118 eggs were measured. The main materials used to build the nests were the saltmarsh plant and mud. Around 60% of nests were degraded or predated. Predation was the main cause of egg loss. Successful nests (with chicks or hatching signs) represented 26% of the total nests monitored. This study reports the first information on the biometry of the species' eggs and nests, confirming the northern coast of Rio de Janeiro state as a nesting area for the species

Values of sleep/wake, activity/rest, circadian rhythms, and fatigue prior to adjuvant breast cancer chemotherapy.

Fatigue is the most prevalent and distressing symptom experienced by patients receiving adjuvant chemotherapy for early stage breast cancer. Higher fatigue levels have been related to sleep maintenance problems and low daytime activity in patients who have received chemotherapy, but knowledge describing these relationships prior to chemotherapy is sparse. The Piper Integrated Fatigue Model guided this study, which describes sleep/wake, activity/rest, circadian rhythms, and fatigue and how they interrelate in women with Stage I, II, or IIIA breast cancer during the 48 hours prior to the first adjuvant chemotherapy treatment. The present report describes these variables in 130 females, mean age=51.4 years; the majority were married and employed. Subjective sleep was measured by the Pittsburgh Sleep Quality Index and fatigue was measured by the Piper Fatigue Scale. Wrist actigraphy was used to objectively measure sleep/wake, activity/rest, and circadian rhythms. Mean Pittsburgh Sleep Quality Index score was 6.73+/-3.4, indicating poor sleep. Objective sleep/wake results were within normal limits established for healthy individuals, except for the number and length of night awakenings. Objective activity/rest results were within normal limits except for low mean daytime activity. Circadian rhythm mesor was 132.3 (24.6) and amplitude was 97.2 (22.8). Mean Piper Fatigue Scale score was 2.56+/-2, with 72% reporting mild fatigue. There were significant relationships between subjective and objective sleep, but no consistent patterns. Higher total and subscale fatigue scores were correlated with most components of poorer subjective sleep quality (r=0.25-0.42, P\u3c or =0.005)

Quantitative MRI can detect subclinical disease progression in muscular dystrophy

Oculopharyngeal muscular dystrophy (OPMD) is a rare autosomal dominant muscular dystrophy with late onset and slow progression. The aim of this study was to compare different methods of quantitative MRI in the follow-up of OPMD to semiquantitative evaluation of MRI images and to functional parameters. We examined 8patients with genetically confirmed OPMD and 5healthy volunteers twice at an interval of 13months. Motor function measurements (MFM) were assessed. Imaging at 1.5T (Siemens Magnetom Avanto) comprised two axial slice groups at the largest diameter of thigh and calf and included T1w TSE, 2-point Dixon for muscular fat fraction (MFF) and a multi-contrast TSE sequence to calculate quantitative T2 values. T1 images were analyzed using Fischer's semiquantitative 5-point (0-4) scale. MFM and visual scores showed no significant difference over the study period. Overall T2 values increased in patients over the study period from 49.4 to 51.6ms, MFF increased from 19.2 to 20.7%. Neither T2 values nor MFF increased in controls. Changes in T2 correlated with the time interval between examinations (r 2=0.42). In this small pilot trial, it was shown that quantitative muscle MRI can detect subclinical changes in patients with OPMD. Quantitative MRI might, therefore, be a useful tool for monitoring disease progression in future therapeutic trial