Miracle-dz/UniFAR-FTUs huggingface dataset:
WASP family proteins and formins compete in pseudopod- and bleb-based migration

Actin pseudopods induced by SCAR/WAVE drive normal migration and chemotaxis in eukaryotic cells. Cells can also migrate using blebs, in which the edge is driven forward by hydrostatic pressure instead of actin. In Dictyostelium discoideum, loss of SCAR is compensated by WASP moving to the leading edge to generate morphologically normal pseudopods. Here we use an inducible double knockout to show that cells lacking both SCAR and WASP are unable to grow, make pseudopods or, unexpectedly, migrate using blebs. Remarkably, amounts and dynamics of actin polymerization are normal. Pseudopods are replaced in double SCAR/WASP mutants by aberrant filopods, induced by the formin dDia2. Further disruption of the gene for dDia2 restores cells’ ability to initiate blebs and thus migrate, though pseudopods are still lost. Triple knockout cells still contain near-normal F-actin levels. This work shows that SCAR, WASP, and dDia2 compete for actin. Loss of SCAR and WASP causes excessive dDia2 activity, maintaining F-actin levels but blocking pseudopod and bleb formation and migration.
Importance of serine727 phosphorylated STAT1 in IFNγ‐induced signaling and apoptosis of human salivary gland cells

Aim: It is reported that in salivary glands of Sjögren’s syndrome (SS), interferon gamma (IFNγ) and IFNγ‐inducible genes containing signal transducers and activators of transcription 1 (STAT1) are upregulated and play a crucial role in the pathogenesis of SS. The aim of this study is to clarify which phosphorylation of STAT1, serine727 (Ser727) or tyrosine701 (Tyr701) of STAT1, is important for IFNγ signaling and IFNγ‐induced apoptosis in salivary gland cells.
LATE EFFECTS OF LEAD POISONING ON MENTAL DEVELOPMENT

FOREWORD The sudden tragic death of Dr. Lord on Jan. 10, 1943 occurred before the completion of the final draft of this paper. It was she who first felt that the minor deviations found on psychologic examination of these children with lead poisoning might be of important significance for the future. It was she who maintained the file of cases, studying them from the psychologic point of view, without encouragement from any one for the first several years. That lead poisoning occurring in early life usually has a disastrous effect on mental development has not been generally recognized, though the subject of lead poisoning in children has been discussed by many observers. The manifestations of acute involvement of the nervous system have been adequately described, and the gross destructive lesions in the brain consequent to acute lead encephalopathy accompanied by cerebral edema and high intracranial pressure have been recognized. On
CYSTIC FIBROSIS OF THE PANCREAS AND ITS RELATION TO CELIAC DISEASE: A CLINICAL AND PATHOLOGIC STUDY

The pathology and pathologic physiology of celiac disease remain obscure in spite of the many attempts that have been made to understand them. It has become clearer in recent years that celiac disease is a clinical picture "characterized by arrest of growth, a distended abdomen, and attacks of diarrhoea with large, pale, foul-smelling stools"1rather than a disease entity and that the underlying pathologic condition may differ in different cases.2A tradition exists that pancreatic steatorrhea can be readily differentiated from idiopathic steatorrhea by the low percentage of split fat in the stools associated with the former and the normal percentage characterizing the latter. A careful survey of the literature, however, reveals few cases of either disease in which careful clinical observations have been followed by adequate postmortem examination. The present study was initiated because of the findings in case 44 (XX), in which a patient with celiac
Bosutinib for the treatment of Philadelphia chromosome-positive leukemias

Introduction: Bosutinib is a dual ABL1 and SRC third-generation tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with chronic myelogenous leukemia (CML) resistant or intolerant to other BCR-ABL1 inhibitors. Bosutinib is active against leukemia cells expressing imatinib-resistant BCR-ABL1 mutations. Mechanistically, this agent may also be beneficial for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) because in preclinical animal models, SRC accelerates ALL disease development. Areas covered: Here, we review the current scientific and medical literature on the role of bosutinib for the treatment of CML. We address the unique therapeutic advantages of this agent, specifically its ability to inhibit mutant BCR-ABL1 kinases conferring resistance to other TKIs and its unique safety profile consisting of mainly manageable self-limited diarrhea, not cardiovascular, side effects. Long-term toxicities reported with dasatinib, nilotinib and ponatinib have not been described with bosutinib. Lastly, we present preclinical data demonstrating that bosutinib inhibits a broader range of tyrosine kinases than any other TKI, including those implicated in acute leukemia. Expert opinion: We propose that future studies should explore the use of bosutinib in Ph+ ALL due to its multi-kinase inhibitory activity and its relatively long-term safety compared with other second- and third-generation TKIs.
Pediatric CT of the Lung: Influences on Image Quality

Objective: To assess influential factors of CT on image quality of the lung in children. Materials and methods: Retrospective evaluation of 82 consecutive chest-CT-scans in 50 children (1-16 years, 17 females and 33 males). Two pediatric radiologists evaluated in consensus the subjective image quality on lung windows using a 4-point scale (1 = very good, 2 = good, 3 = moderate, 4 = poor). Ventilation, motion artifacts and beam hardening artifact were included in this score. The effects of the following factors were evaluated: 1) CT-settings (tube energy, tube current); 2) Patient’s age, weight, chest size, ventilation; 3) Artifacts of devices, tubes and lines; 4) Combination MRI of the abdomen prior to CT of the chest with the same sedation/anesthesia in oncological patients. Results: The odds of having a better image quality increase with patient’s age, weight and chest diameter in a multiple-factor model. There was no difference between tube current protocols. In infants (15 kg) subjective image quality was good in only 1 (8%), moderate in 8 (67%) and poor in 3 (25%) scans. In childhood and adolescence (15 - 90 kg) 25 (36%) scans were very good, 28 (40%) good, 15 (21%) moderate and 2 (3%) poor. Artifacts of tubes and lines have no statistical significant influence on image quality. Lower lung densities were related to better ventilation and older children. Conclusion: Increasing dose parameters may not increase necessarily subjective image quality in infants (15 kg), rather than good ventilation, optimal preparation and avoiding artifacts. A possible explanation of the rather moderate image quality in infants may be the alveolar stage of the lung. Up to two years of age the lung has a high specific lung volume per kg and a low total lung volume with a low alveolar surface.
A Conceptual Model of Weight Loss and Weight Regain: An Intervention for Change

Obesity is considered one of the most prevalent health problems in the United States. The controversy surrounding the causes of obesity and its incidence of illness as well as the less-than-promising statistics for long-term weight loss raise questions about present treatment modalities. Statistics indicate that the majority of persons who lose weight regain the weight within 1 to 5 years. Statistics also indicate that 95% of the participants in weight loss programs are women. Based on the findings of a qualitative study, Wysoker developed a model of weight loss and weight regain. The model offers a framework for treatment and includes three different approaches: (a) one can lose weight and keep it off; (b) it may be impossible to lose weight and keep it off; and (c) women will continue to try to lose weight, despite the long history of losing weight and gaining the lost weight back.
Rates of HIV testing and diagnosis in South Africa: successes and challenges

Background:UNAIDS aims for 90% of HIV-positive individuals to be diagnosed by 2020, but few attempts have been made in developing countries to estimate the fraction of the HIV-positive population that has been diagnosed. Methods:To estimate the rate of HIV diagnosis in South Africa, reported numbers of HIV tests performed in the South African public and private health sectors were aggregated, and estimates of HIV prevalence in individuals tested for HIV were combined. The data were integrated into a mathematical model of the South African HIV epidemic, which was additionally calibrated to estimates of the fraction of the population ever tested for HIV, as reported in three national household surveys. Results:The fraction of HIV-positive adults who were undiagnosed declined from more than 80% in the early 2000s to 23.7% [95% confidence interval (95% CI) 23.1–24.3] in 2012. The undiagnosed proportion in 2012 was substantially higher in men (31.9%, 95% CI 29.7–34.3) than in women (19.0%, 95% CI 17.9–19.9). Projected probabilities of experiencing disease progression (CD4+ cell count <350 cells/&mgr;l) without diagnosis are more than 50% for most HIV-positive adults over the age of 40. The fraction of HIV-positive adults who are undiagnosed is projected to decline to 8.9% by 2020 if current targets (10 million tests per annum) are met. Conclusion:South Africa has made significant progress in expanding access to HIV testing, and at current testing rates, the target of 90% of HIV-positive adults diagnosed by 2020 is likely to be reached. However, uptake is relatively low in men and older adults.
Reconstitution and functional characterization of ion channels from nanodiscs in lipid bilayers

Recent studies have shown that membrane proteins can be efficiently synthesized in vitro before spontaneously inserting into soluble nanoscale lipid bilayers called nanodiscs (NDs). In this paper, we present experimental details that allow a combination of in vitro translation of ion channels into commercially available NDs followed by their direct reconstitution from these nanobilayers into standard bilayer setups for electrophysiological characterization. We present data showing that two model K+ channels, Kcv and KcsA, as well as a recently discovered dual-topology F− channel, Fluc, can be reliably reconstituted from different types of NDs into bilayers without contamination from the in vitro translation cocktail. The functional properties of Kcv and KcsA were characterized electrophysiologically and exhibited sensitivity to the lipid composition of the target DPhPC bilayer, suggesting that the channel proteins were fully exposed to the target membrane and were no longer surrounded by the lipid/protein scaffold. The single-channel properties of the three tested channels are compatible with studies from recordings of the same proteins in other expression systems. Altogether, the data show that synthesis of ion channels into NDs and their subsequent reconstitution into conventional bilayers provide a fast and reliable method for functional analysis of ion channels.
A Meta-Analysis of Competition in Field Experiments

A meta-analysis was conducted on field-competition experiments published in six journals over a 10-yr period. We analyzed the effects of competition on the biomass of organisms belonging to 93 species in a wide variety of habitats. Competition had a large effect overall, with a great deal of heterogeneity in that effect among organisms. There were large differences among trophic levels in competitive effects, but the relative magnitude of competition at different trophic levels was contrary to the predictions of ecological theory. Primary producers and carnivores displayed small to medium effects. In these two groups, interspecific effects did not differ from intraspecific effects, nor did effects differ in terrestrial versus aquatic habitats. The effects of competition on herbivores ranged from large effects on anurans and lotic arthropods, to medium effects on marine mollusks and echinoderms, to effects that were not statistically distinguishable from zero for terrestrial arthropods. Interspecific competitive effects among these herbivore groups were generally less than intraspecific effects. Among primary producers, the effects of competition were not different in high- and low-productivity habitats. Across all taxa, large organisms did not experience greater competitive effects than small organisms, and competitive effects did not depend on the size attained in the absence of competitors. The effects of competition were weakly density-dependent in cases in which it was possible to examine the effects of the density of neighbors. Experiments conducted on caged organisms resulted in greater competitive effects than those with free-roaming and unenclosed organisms. Experiments with small sample sizes, short durations, and poor experimental design were more variable than experiments that were larger, longer, and better planned.
Independent Versus Nonindependent Mate Choice: Do Females Copy Each Other?

There is increasing evidence from both observational and experimental studies that females may copy each other's mating decisions. Female copying can be defined as a type of nonindependent choice in which the probability that a female chooses a given male increases if other females have chosen that male and decreases if they have not. The important characteristic of copying behavior that separates it from other similar processes is that the change in the probability of choice is strictly because of the actions of other females and not the consequences of those actions (e.g., a male's behavior changing as a result of successful matings). A gametheory model suggests that the adaptive significance of female copying may depend primarily on the ratio of the costs to the benefits of active mate choice. Copying behavior, and more generally conspecific cueing, may be important in many behavioral processes beyond mate choice.
How do age and tooth loss affect oral health impacts and quality of life? A study comparing two national samples.

Abstract – Age and loss of teeth can be expected to have a complex relationship with oral health-related quality of life. This study aimed to explain how age and tooth loss affect the impact of oral health on daily living using the short form, 14-item Oral Health Impact Profile (OHIP-14) on national population samples of dentate adults from the UK (1998 UK Adult Dental Health Survey) and Australia (1999 National Dental Telephone Interview Survey). After correcting for key covariables, increasing age was associated with better mean impact scores in both populations. Those aged 30–49 years in Australia showed the worst (highest) scores. In the UK, those aged under 30 showed the highest scores. In both countries, adults aged 70+ showed much better scores than the rest (P < 0.001). When corrected for age, the independent effect of tooth loss was that the worst scores were found where there were fewer than 17 natural teeth in the UK and fewer than 21 teeth in Australia. People with 25 or more teeth averaged much better scores than all other groups (P < 0.001), although there were differences in pattern between countries. When Australians were analysed by region of birth, the pattern of scores by tooth loss for British/Irish immigrants was strikingly similar to that for the UK sample. First-generation immigrants from elsewhere showed much worse overall scores and a profoundly different pattern to the Australian- and British-born groups. Age, number of teeth and cultural background are important variables influencing oral health-related quality of life.
Towards a Measurement of Paraspinal Soft Tissue Mobility: Development of a Method and Preliminary Results

AbstractThe purpose of this study was to determine if the mobility of soft tissues in theparaspinal region is measurable in vivo, and to test the feasibility of obtaining useful data with a newly developed method. A small handheld device was developed to apply and measure oblique forces to the paraspinal tissues, resulting in gliding, which was measured using videoanalysis. Forces were transmitted to the tissues through disks adhered to the skin. The tissue mobility at the levels T8-9 and L1-2 was measured in four directions (cranial-caudal, and medial-lateral). Soft tissue mobility was measured in 16 subjects and the obtained force-displacement curves were representative for visco-elastic tissues. The range of motion (ROM) at 4 kg load in the 4 directions showed a consistent pattern, with soft tissues gliding most medially (5.64 ± 0.58 cm), followed by cranially (4.30 ± 0.48 cm), laterally (3.50 ± 0.46 cm) and caudally (2.68 ± 0.49 cm), at the thoracic level. The pattern at the lumbar level was similar a.
Non-R5-tropic HIV-1 in subtype A1 and D infections were associated with lower pretherapy CD4+ cell count but not with PI/(N)NRTI therapy outcomes in Mbarara, Uganda

Background:Previous studies suggest that infection with non-R5-tropic subtype B HIV-1, compared with R5, is associated with a more rapid decline in CD4+ cell count, but does not affect PI/(N)NRTI therapy outcome. Here, we explored clinical correlates associated with viral tropism in subtype A1 and D infections. Methods:HIV-1 subtype A1 (n = 196) and D (n = 143) pretherapy plasma samples and up to 7.5 years of posttherapy virologic and CD4+ data were collected from a cross-sectional cohort in Mbarara, Uganda. Tropism and subtype were inferred using env V3 (geno2pheno) and gp41 (RIP) Sanger sequences. For each subtype, R5 infection was compared with non-R5 in terms of: pretherapy viral load and CD4+ cell count (Mann–Whitney tests), and therapy outcomes, including time to virologic suppression, postsuppression virologic rebound, CD4+ decline and CD4+ recovery (log-rank tests). Results:A 94% of all patients in this study achieved virologic suppression within median 3 months posttherapy. In both subtypes, non-R5 infection was associated with lower pretherapy CD4+ cell count (non-R5 vs. R5; A: median 57 vs. 147 cells/&mgr;l P = 0.005; D: 80 vs. 128 cells/&mgr;l P = 0.006). Multivariable linear regression confirmed that tropism, not subtype nor the interaction between subtype and tropism, was a significant predictor of pretherapy CD4+ cell count (P < 0.0001). None of pretherapy viral load, time to virologic suppression, virologic rebound, CD4+ decline nor CD4+ recovery was significantly different (all P > 0.09). Conclusion:Regardless of HIV-1 subtype or tropism, the majority of patients in this Ugandan cohort responded to therapy, even though non-R5 infection was associated with lower pretherapy CD4+ cell count.
The effects of HIV on fertility by infection duration: evidence from African population cohorts before antiretroviral treatment availability.

OBJECTIVES To estimate the relationship between HIV natural history and fertility by duration of infection in east and southern Africa before the availability of antiretroviral therapy and assess potential biases in estimates of age-specific subfertility when using retrospective birth histories in cross-sectional studies. DESIGN Pooled analysis of prospective population-based HIV cohort studies in Masaka (Uganda), Kisesa (Tanzania) and Manicaland (Zimbabwe). METHODS Women aged 15-49 years who had ever tested for HIV were included. Analyses were censored at antiretroviral treatment roll-out. Fertility rate ratios were calculated to see the relationship of duration of HIV infection on fertility, adjusting for background characteristics. Survivorship and misclassification biases on age-specific subfertility estimates from cross-sectional surveys were estimated by reclassifying person-time from the cohort data to simulate cross-sectional surveys and comparing fertility rate ratios with true cohort results. RESULTS HIV-negative and HIV-positive women contributed 15 440 births and 86 320 person-years; and 1236 births and 11 240 000 person-years, respectively, to the final dataset. Adjusting for age, study site and calendar year, each additional year since HIV seroconversion was associated with a 0.02 (95% confidence interval 0.01-0.03) relative decrease in fertility for HIV-positive women. Survivorship and misclassification biases in simulated retrospective birth histories resulted in modest underestimates of subfertility by 2-5% for age groups 20-39 years. CONCLUSION Longer duration of infection is associated with greater relative fertility reduction for HIV-positive women. This should be considered when creating estimates for HIV prevalence among pregnant women and prevention of mother-to-child transmission need over the course of the HIV epidemic and antiretroviral treatment scale up.
Chick Begging Strategies in Relation to Brood Hierarchies and Hatching Asynchrony

Altricial offspring solicit food by begging, and their parents feed them according to begging intensity, which has been shown to be positively related to offspring need. Parent‐offspring genetic conflict calls for analyses of evolutionary stability, and various theoretical models have shown that stability is possible in the framework of handicap theory. The models predict that a negative relationship exists between offspring condition and begging and that offspring in poorer condition should be fed preferentially. However, these predictions depend on two unsatisfactory assumptions. First, they assume a monotonically decelerated relation between condition and fitness (this function is more likely to be sigmoid); second, they ignore physical competition between siblings, which is known to be important. We examined the significance of these issues by manipulating hatching asynchrony in broods of starlings Sturnus vulgaris, thus controlling competitive asymmetries between nest mates. We created broods with senior (older) and junior (younger) chicks and control broods with synchronous chicks. In field and laboratory experiments, we found that seniors begged less than juniors and controls, whereas juniors did not differ significantly from controls. However, seniors received more food from their parents and grew better than juniors or controls (hence, they were in better condition). These results violate the predictions of available theoretical models and, together with limitations in the universality of their assumptions, indicate that fundamental aspects of parent‐offspring communication are not yet understood.
Investment Strategies of Breeders in Avian Cooperative Breeding Systems

An individual's optimal investment in young depends partly on the number of individuals caring for the same brood. In cooperative breeders, the investment strategy of parents with helpers is variable. When parents maintain the same effort regardless of helper number, helper care is additive. When parents fully compensate for the care of helpers by decreasing their own effort, total care does not increase. A study of long‐tailed tits Aegithalos caudatus showed that both parental strategies may occur within a species, depending on the number of helpers. A comparative analysis of 27 cooperative breeders was conducted to test the predictions of a graphical model that care is additive when nestling starvation is frequent and parents exhibit compensatory reductions in care when starvation is rare. Both predictions were supported. In this interspecific comparison, a species' mean group size was not associated with compensatory responses by parents. There was some evidence that males and females had different investment rules. Males tended to show compensatory reductions in care when adult survival rate was low. In contrast, while both sexes showed compensation when nestling starvation was infrequent, this association was significant only for females.