Notes

An Atypical Indication of Mycobacterium tb Infection.
Finally, by increasing alignment sensitivity from the default baseline, parameter tuning can increase the number of noncoding sites that can be scored for conservation by over 76%. Overall, tuning of masking and alignment parameters can generate optimized multiple alignments to drive biological discovery in plants.Transgene technology is valuable and helpful in many fields, including basic medical and biological research, biotechnology, and therapy. Recent advances in targeting technology accelerate the production of transgenic plants and animals and the application for gene therapy. To develop the technology, we examine the utility as the new safe harbor locus, l-gulono-γ-lactone oxidase (Gulo) locus in human and mice. We performed experiments in vitro and in vivo knockout and knockin mouse and cell lines to validate their applicability using these loci. The Gulo locus might be good candidates for safe harbor loci for transgenic research.Some 2,4-disubstituted quinazolines were synthesized and studied as multidrug resistance (MDR) reversers. The new derivatives carried the quinazoline-4-amine scaffold found in modulators of the ABC transporters involved in MDR, as the TKIs gefitinib and erlotinib. Their behaviour on the three ABC transporters, P-gp, MRP1 and BCRP, was investigated. Almost all compounds inhibited the P-gp activity in MDCK-MDR1 cells overexpressing P-gp, showing EC50 values in the nanomolar range (1 d, 1 e, 2 a, 2 c, 2 e). Some compounds were active also towards MRP1 and/or BCRP. Docking results obtained by in silico studies on the P-gp crystal structure highlighted common features for the most potent compounds. The P-gp selective compound 1 e was able to increase the doxorubicin uptake in HT29/DX cells and to restore its antineoplastic activity in resistant cancer cells in the same extent of sensitive cells. Compound 2 a displayed a dual inhibitory effect showing good activities towards both P-gp and BCRP.The phrase 'person-centred care' (PCC) reminds us that the fundamental philosophical goal of caring for people is to uphold or promote their personhood. However, such an idea has translated into promoting individualist notions of autonomy, empowerment and personal responsibility in the context of consumerism and neoliberalism, which is problematic both conceptually and practically. From a conceptual standpoint, it ignores the fact that humans are social, historical and biographical beings, and instead assumes an essentialist or idealized concept of personhood in which a person is viewed as an individual static object. From a practical standpoint, the application of such a concept of personhood can lead to neglect of a person's fundamental care needs and exacerbate the problems of social inequity, in particular for older people and people with dementia. Therefore, we argue that our understanding of PCC must instead be based on a dynamic concept of personhood that integrates the relevant social, relational, temporal and biographical dimensions. We propose that the correct concept of personhood in PCC is one in which persons are understood as socially embedded, relational and temporally extended subjects rather than merely individual, autonomous, asocial and atemporal objects. We then present a reconceptualization of the fundamental philosophical goal of PCC as promoting selfhood rather than personhood. Such a reconceptualization avoids the problems that beset the concept of personhood and its application in PCC, while also providing a philosophical foundation for the growing body of empirical literature that emphasizes the psychosocial, relational, subjective and biographical dimensions of PCC.
While brains of patients with Alzheimer's disease and related tauopathies have evidence of altered RNA processing, we lack a mechanistic understanding of how altered RNA processing arises in these disorders and if such changes are causally linked to neurodegeneration.

Using Drosophila melanogaster models of tauopathy, we find that overall activity of nonsense-mediated mRNA decay (NMD), a key RNA quality-control mechanism, is reduced. Genetic manipulation of NMD machinery significantly modifies tau-induced neurotoxicity, suggesting that deficits in NMD are causally linked to neurodegeneration. Mechanistically, we find that deficits in NMD are a consequence of aberrant RNA export and RNA accumulation within nuclear envelope invaginations in tauopathy. We identify a pharmacological activator of NMD that suppresses neurodegeneration in tau transgenic Drosophila, indicating that tau-induced deficits in RNA quality control are druggable.

Our studies suggest that NMD activators should be explored for their potential therapeutic value to patients with tauopathies.
Our studies suggest that NMD activators should be explored for their potential therapeutic value to patients with tauopathies.Asymmetric competition occurs when some species have distinct advantages over their competitors and is common in animals with overlapping habitats and diet. However, the mechanism allowing coexistence between asymmetric competitors is not fully clear. Chinese white-bellied rats (Niviventer confucianus, CWR) and Korean field mice (Apodemus peninsulae, KFM) are common asymmetric competitors in shrublands and forests west of Beijing city. They share similar diet (e.g. plant seeds) and activity (nocturnal), but differ in body size (CWR are bigger than KFM), food hoarding habit (CWR mainly larder hoarding; KFM both larder and scatter hoarding), and ability to protect cached food (CWR are more aggressive than KFM). Here, we tested seed competition in 15 CWR-KFM pairs over a 10-day period under semi-natural enclosure conditions to uncover the differences in food hoarding, cache pilferage, and food protection between the 2 rodents, and discuss the implication for coexistence. Prior to pilferage, CWR harvested and atergy than the dominant species (i.e. CWR), and may contribute to their coexistence in the field.Gesture is an important communication tool that provides insight into infants' early language and cognitive development and predicts later language skills. While bilingual school-age children have been reported to gesture more than monolinguals, there is a lack of research examining gesture use in infants exposed to more than one language. In this preregistered study, we compared three groups of 14-month-old infants (N = 150) learning French and/or English bilinguals (hearing a second language at least 25% of the time), exposed (hearing a second language 10%-24% of the time), and monolinguals (hearing one language 90% of the time or more). Parent-reported use of communicative gestures was gathered from the MacArthur-Bates Communicative Development Inventories (CDI). Results showed that the three language groups had similarly sized gesture repertoires, suggesting that language exposure did not affect gesture development at this age. However, a gender effect was found, where girls produced more types of gestures than boys. Overall, these results suggest that gender, but not language exposure, contributes to differences in gesture development in infancy.
The aim of this study was to review bariatric procedure outcomes among patients with Prader-Willi syndrome (PWS), melanocortin 4 receptor (MC4R) mutations, Bardet-Biedl syndrome, and hypothalamic obesity.

Systematic published literature review used the following search terms "Prader-Willi syndrome," "Bardet-Biedl syndrome," "hyperphagia," "bariatric surgery," "MC4R"/"melanocortin 4 receptor", "hypothalamic obesity," and "bariatric procedure." Information collected included demographics, genetics, anthropometry, procedure type, outcomes, and complications, with inclusion of case series and clinical reports given the rarity of the disorders. For PWS, postoperative weight-change percentage and BMI up to 14 years following surgery were analyzed using general linear mixed models, with descriptive outcomes for other conditions.

A total of 54 publications were identified, with variable follow-up periods for 202 patients (114 with PWS, 43 with MC4R mutations, 7 with Bardet-Biedl syndrome, and 38 with hypothalamic obesity) among bariatric procedures. Weight loss of patients with PWS was greatest within 1 year of surgery, with weight-change percentage not significantly different from 0 at 5 years. Long-term results in other conditions were variable and featured suboptimal weight loss and increased reoperation risk.

Bariatric procedures among hyperphagic individuals, including those with PWS, report variable results and outcomes. Benefits of bariatric surgery may be less durable in hyperphagic disorders in comparison with other patients with severe obesity.
Bariatric procedures among hyperphagic individuals, including those with PWS, report variable results and outcomes. Benefits of bariatric surgery may be less durable in hyperphagic disorders in comparison with other patients with severe obesity.
It is necessary to comprehensively consider the personal and environmental factors of women who experience overweight or obesity and low-income households (WOOL) to improve their quality of life (QoL).

The aim of this study was to test a hypothetical path model to estimate the effects of self-efficacy, psychological distress, social support, and health-promoting behaviors (HPB) on QoL and verify the mediating effects of HPB among WOOL.

A total of 151 women with a monthly household income less than 50% of the national median income at eight welfare centers in South Korea participated in this study. Data were collected from January to December 2019 and analyzed using SPSS 25.0 and Amos 23.0.

The fit indices of the model were adequate (χ
=0.197, p=.657; normed χ
=0.197, GFI=0.999, CFI=1.000, NFI=0.999, TLI=1.000, RMSEA=0.000, and SRMR=0.005). Self-efficacy had significant indirect and total effects on QoL (β=0.064, p=.004, 95% CI [0.015, 0.139]; β=0.064, p=.004, 95% CI [0.015, 0.139]). HPB completely mediated the path of self-efficacy to QoL. Social support had significant total, direct, indirect, and total effects on QoL (β=0.326, p=.001, 95% CI [0.010, 0.025]; β=0.047, p=.015, 95% CI [0.008, 0.120]; β=0.373, p=.001, 95% CI [0.015, 0.369]). HPB partially mediated the path of social support to QoL. Psychological distress had significant direct effects on QoL (β=-0.307, p=.001, 95% CI [-0.022, -0.007]). Self-efficacy, psychological distress, social support, and HPB explained 42.3% of the total variance in QoL.

Integrated nursing interventions that consider self-efficacy, psychological distress, social stress, and HPB can be useful for improving the QoL of WOOL.
Integrated nursing interventions that consider self-efficacy, psychological distress, social stress, and HPB can be useful for improving the QoL of WOOL.Komagataella phaffii (a.k.a. Pichia pastoris) requires histidine for optimal growth when cultured in a medium containing yeast extract, peptone (YP), and acetate (YPA). Ubiquitin inhibitor We demonstrate that HIS4-deficient, K. phaffii strain GS115 exhibits a growth defect on YP-media containing acetate, but not on other carbon sources. K. phaffii X33, a prototroph, grows better than K. phaffii GS115 (his4), a histidine auxotroph in YPA. Normal growth of GS115 is restored either by the expression of HIS4 or by culturing in YPA containing ≥0.6 mM histidine. In the presence of histidine, expression of several genes is altered, including those encoding key subunits of mitochondrial ATP synthase, transporters of amino acids and nutrients, as well as biosynthetic enzymes. Thus, histidine should be included as an essential component for optimal growth of K. phaffii histidine auxotrophs cultured in YPA.
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