Miracle-dz/UniFAR-FTUs huggingface dataset:
Notch1 Signaling Regulates Wound Healing via Changing theCharacteristics of Epidermal Stem Cells

During wound healing and reconstruction, epidermal stem cells (ESCs) migrate to the wound site and activate to repair the damaged epithelium. Moreover, there exist complicate signaling pathways to regulate wound regeneration including Notch signaling. The Notch signaling pathway is a regulator of epidermal differentiation, which may be an important mediator of wound regeneration that participates in various processes, from the development of the dermis to the formation of skin appendages. Here, we show that Notch signaling pathways are upregulated by Jagged1 in ESCs and stem cell characteristics of ESCs change when Notch1 signaling varies. By administration of siRNAJagged1 knockdown ESCs in wounds, we observe that the suppression of Jagged1 down regulate expression of Notch signaling and resulted in poor-quality wound healing. Connecting Notch1 pathways activity to ESCs response to wound repairing may develop a new therapeutic strategy for delayed healing.
Depth-related patterns of coral recruitment and cryptic suspension-feeding invertebrates on Guana Island, British Virgin Islands

Scleractinian coral recruitment is known to vary at a variety of spatial scales, from centimeters to hundreds of kilometers. This study examined patterns of coral recruitment and cryptic space utilization on artificial settlement plates over three depths (6, 15 and 24 m) and at two reefs on Guana Island (18°N), British Virgin Islands. Brooding corals (mostly Agaricia spp. with some Porites spp.) dominated recruitment patterns. On both reefs, recruitment was cryptic (on bottom or side of plates) at all depths and consistently low at 24 m where a diverse assemblage of suspension-feeding invertebrates monopolized settlement space on the bottom of plates. At 6 and 15 m depth, coral recruitment was high, but varied among groups of plates spaced several meters apart. Extrapolation from the shallow recruitment rate to a m 2 area reveals the highest recorded recruitment rate (333 recruits m -2 yr -1 ) on plates in the Caribbean region. Analyses of space use on bottom surfaces of plates left in-situ for 2 yrs showed that area suitable for coral settlement (predominantly crustose coralline algae) declined with depth. Encrusting sponges did not vary consistently among the three depths, but the cover of bivalves (mostly Spondylus americanus) increased significantly at 24 m accounting for a large portion of occupied space. There was a significant positive relationship between settlement area on bottom surfaces of plates and coral recruitment (r =0.306), yet there was also variation in recruitment between depths and among racks that remained unexplained by available settlement area. The patterns of coral recruitment and space occupation by potential competitors are consistent with an emerging view that benthic interactions effect recruitment patterns when space is limiting, yet supply-side processes or very early benthic mortality is driving spatial variability in recruitment when space is abundant.
Sequences in the cytoplasmic tail of SARS-CoV-2 spike facilitate syncytia formation

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds the cell surface protein ACE2 to mediate fusion of the viral membrane with target cells1–4. S comprises a large external domain, a transmembrane domain (TMD) and a short cytoplasmic tail5,6. To elucidate the intracellular trafficking of S protein in host cells we applied proteomics to identify cellular factors that interact with its cytoplasmic tail. We confirm interactions with components of the COPI, COPII and SNX27/retromer vesicle coats, and with FERM domain actin regulators and the WIPI3 autophagy component. The interaction with COPII promotes efficient exit from the endoplasmic reticulum (ER), and although COPI-binding should retain S in the early Golgi system where viral budding occurs, the binding is weakened by a suboptimal histidine residue in the recognition motif. As a result, S leaks to the surface where it accumulates as it lacks an endocytosis motif of the type found in many other coronaviruses7,8. It is known that when at the surface S can direct cell:cell fusion leading to the formation of multinucleate syncytia9–11. Thus, the trafficking signals in the cytoplasmic tail of S protein indicate that syncytia formation is not an inadvertent by-product of infection but rather a key aspect of the replicative cycle of SARS-CoV-2 and potential cause of pathological symptoms.
How Euglena gracilis swims: flow field reconstruction and analysis

Euglena gracilis is a unicellular organism that swims by beating a single anterior flagellum. We study the nonplanar waveforms spanned by the flagellum during a swimming stroke, and the three-dimensional flows that they generate in the surrounding fluid. Starting from a small set of time-indexed images obtained by optical microscopy on a swimming Euglena cell, we construct a numerical interpolation of the stroke. We define an optimal interpolation (which we call synthetic stroke) by minimizing the discrepancy between experimentally measured velocities (of the swimmer) and those computed by solving numerically the equations of motion of the swimmer driven by the trial interpolated stroke. The good match we obtain between experimentally measured and numerically computed trajectories provides a first validation of our synthetic stroke. We further validate the procedure by studying the flow velocities induced in the surrounding fluid. We compare the experimentally measured flow fields with the corresponding quantities computed by solving numerically the Stokes equations for the fluid flow, in which the forcing is provided by the synthetic stroke, and find good matching. Finally, we use the synthetic stroke to derive a coarse-grained model of the flow field resolved in terms of a few dominant singularities. The far field is well approximated by a time-varying Stresslet, and we show that the average behavior of Euglena during one stroke is that of an off-axis puller. The reconstruction of the flow field closer to the swimmer body requires a more complex system of singularities. A system of two Stokeslets and one Rotlet, that can be loosely associated with the force exerted by the flagellum, the drag of the body, and a torque to guarantee rotational equilibrium, provides a good approximation.
Preliminary evidence for upward elevational range shifts by Eastern Himalayan birds

The ongoing climate crisis is one of the most significant threats to biodiversity globally. As the Earth warms, species have adapted by shifting their geographical ranges either polewards, or in mountainous regions, upslope towards higher elevations, presumably to continue to inhabit a suitable thermal environment. Upslope range shifts are of particular concern in tropical mountain ranges because: (a) tropical species are particularly thermally sensitive, (b) as species move upwards, they can run out of habitable space, leading to local extirpations, and (c) tropical mountains harbour a disproportionately high fraction of the planet’s terrestrial biodiversity – rapid upslope range shifts can therefore result in significant biodiversity losses. We used citizen science data over a 13-year period to evaluate whether 39 eastern Himalayan bird species might be shifting to higher elevations over time, by analyzing changes in the frequency of reporting of these species at birdwatching hotspots. For these species, we find evidence consistent with upslope range shifts, with species with the bulk of their elevational ranges below the hotspot elevation showing increases in their reporting frequency over time, and those with most of their elevational ranges above the hotspot elevation declining in reporting frequency. Our findings are suggestive of rapid responses to climate change by eastern Himalayan birds. We caution that eastern Himalayan bird species might be at special risk from increasing global temperatures because of their heightened thermal sensitivity coupled with particularly high rates of warming in the region. Eastern Himalayan birds are likely to require large tracts of undisturbed natural habitat across entire elevational gradients to be able to track changing temperatures by moving to higher elevations to remain resilient to climate change. SUMMARY One of the most fundamental responses of species to changing temperatures is to change their geographic ranges, possibly to track the range of temperatures that is ideal for their survival. With increasing climate warming, this shift could happen by moving towards the poles or in mountainous areas, towards the summit. Due to the high thermal sensitivity of tropical species and the decrease in space as species move up mountains, the extremely biodiverse bird communities of tropical mountains are particularly vulnerable. Using citizen science data from birding hotspots along an elevational gradient in the Eastern Himalayas over a 13-year period, we measured the change in reporting frequency of 39 common bird species. Changes in reporting frequency are generally consistent with the fact that upslope shifts are taking place in the Eastern Himalayas, similar to results for birds from other tropical mountains.
Enhanced Loading of Paclitaxel in Cationic Liposomes by Replacement of Oleoyl with Linoleoyl Lipid Tails with Benefits in Cancer Therapeutics from In Vitro Studies

Lipid-based carriers of the hydrophobic drug paclitaxel (PTX) are used in clinical trials as next-generation agents for cancer chemotherapy. Improving the loading capacity of these carriers requires enhanced PTX solubilization. We compared the solubility of PTX in cationic liposomes (CLs) with lipid tails containing one (oleoyl; C18:1 Δ9; DOTAP/DOPC) or two (linoleoyl; C18:2 Δ9; DLinTAP/DLinPC) cis double bonds with newly synthesized cationic DLinTAP (2,3-dilinoleoyloxypropyltrimethylammonium methylsufate). We used differential-interference-contrast microscopy to directly observe PTX crystal formation and generate kinetic phase diagrams representing the time-dependence of PTX solubility as a function of PTX content in the membrane. Replacing tails bearing one cis double bond (DO lipids) with those bearing two (DLin lipids) significantly increased PTX membrane solubility in CLs. Remarkably, 8 mol% PTX in DLinTAP/DLinPC CLs remained soluble for approximately as long as 3 mol% PTX (the membrane solubility limit which has been the focus of most previous fundamental studies and clinical trials) in DOTAP/DOPC CLs. The large increase in solubility is likely caused by enhanced molecular affinity between lipid tails and PTX upon replacement of oleoyl by linoleoyl tails, rather than by the transition in membrane structure from lipid bilayers to inverse cylindrical micelles observed in small-angle X-ray scattering. Importantly, the efficacy of PTX-loaded CLs against human prostate cancer (PC3) cells from measurements of the IC50 of PTX cytotoxicity was unaffected by changing the lipid tails, and toxicity of the CL carrier alone was negligible. Moreover, efficacy was approximately doubled against human melanoma (M21) cells for PTX-loaded DLinTAP/DLinPC over DOTAP/DOPC CLs. The findings demonstrate the potential of chemical modifications of the lipid tails to increase the PTX membrane loading well over the typically used 3 mol% while maintaining (and in some cases even increasing) the efficacy of CLs. The increased PTX solubility will aid the development of liposomal PTX carriers that require significantly less lipid to deliver a given amount of PTX, reducing side effects and costs.
Extended and dynamic linker histone-DNA interactions control chromatosome compaction

Chromatosomes, composed of nucleosomes and linker histones, play a fundamental role in chromatin regulation. However, a detailed understanding of their structure is lacking, partially due to their complex dynamics. Using single-molecule DNA unzipping with optical tweezers to map histone-DNA interactions in the chromatosome, we reveal a symmetrical compaction of the nucleosome core, governed by the linker histone globular domain contacts at the dyad. Dynamic mapping revealed that the C-terminal domain binds both DNA linkers, at ~ ±115 and ~ ±140 bp from the dyad, to compact the nucleosome entry and exit. Although H1 interacts more transiently with one linker, these dynamic contacts are crucial for stabilizing the binding to the second one. Extensive unzipping of the linker DNA, which mimics its invasion by motor proteins, shifts H1 off the dyad, triggering nucleosome decompaction. Our findings reveal molecular details of chromatosome compaction and its potential modulation by the transcription machinery.
A systematic review and meta-analysis for association of Helicobacter pylori colonization and celiac disease

Background and objectives Based on some previous observational studies there is a theory that suggests a potential relationship between Helicobacter pylori (H. pylori) colonization and celiac disease (CD), however, the type of this relationship is still controversial. Therefore, we aimed to conduct a systematic review and meta-analysis to explore all related primary studies to find any possible association between CD and human H. pylori colonization. Data sources Studies were systematically searched and collected from four databases and different types of gray literature to cover all available evidence. After screening, the quality and risk of bias assessment of the selected articles were evaluated. Synthesis methods Meta-analysis calculated pooled odds ratio (OR) on the extracted data. Furthermore, heterogeneity, sensitivity, subgroups, and publication bias analyses were assessed. Results Twenty-four studies were included in this systematic review, with a total of 5241 cases and 132947 control people. The results of meta-analysis on 24 studies showed a significant and negative association between H. pylori colonization and CD (pooled OR= 0.58; 95% CI = 0.45 - 0.76; P < 0.001), with no publication bias (P = 0.407). The L’Abbé plots also showed a trend of having more H. pylori colonization in the control group. Among subgroups, ORs were notably different only when the data were stratified by continents or risk of bias; however, subgroup analysis could not determine the source of heterogeneity. Conclusions According to the meta-analysis, H. pylori has a mild protective role toward CD. Although this negative association is not strong, it is statistically significant and should be further considered. Further investigations in both molecular and clinic fields with proper methodology and more detailed information are needed to discover more evidence and underlying mechanisms to clear the interactive aspects of H. pylori colonization in CD patients. Systematic review registration number (PROSPERO) CRD42020167730
‘At the point of confluence of sociology and Indology’: Louis Dumont’s postulate reconsidered

In this article, I aim to show how Louis Dumont’s famous claim that ‘the condition for a sound development of Sociology of India is found in the establishment of the proper relation between it and classical Indology’ has become obsolete and was from the beginning a problematic postulate. I first develop the historical background of the denigration of anthropological approaches in India against the rise of an idealising Indology as a philological discipline. Then I discuss the structural, methodological and ideological problems that made it difficult to follow Dumont’s advice to search for the point of confluence of sociology and Indology. Finally, I place Dumont’s holistic approach in relation to the holistic structure of academic disciplines that emerged in the 19th century on the basis of the nation-state model and argue that it is misleading and reductive to think that ‘the construction of an Indian Sociology rests in part upon the existence of Indology’.
Selective attention modulates neural envelope tracking of informationally masked speech in healthy older adults

Speech understanding in noisy situations is compromised in old age. This study investigated the energetic and informational masking components of multi-talker babble noise and their influence on neural tracking of the speech envelope in a sample of healthy older adults. Twenty-three older adults (age range 65 - 80 years) listened to an audiobook embedded in noise while their electroencephalogram (EEG) was recorded. Energetic masking was manipulated by varying the signal-to-noise ratio (SNR) between target speech and background talkers and informational masking was manipulated by varying the number of background talkers. Neural envelope tracking was measured by calculating temporal response functions (TRFs) between speech envelope and EEG. Number of background talkers, but not SNR modulated the amplitude of an earlier (around 50 ms time lag) and a later (around 300 ms time lag) peak in the TRFs. Selective attention, but not working memory or peripheral hearing additionally modulated the amplitude of the later TRF peak. Finally, amplitude of the later TRF peak was positively related to accuracy in the comprehension task. The results suggest that stronger envelope tracking is beneficial for speech-in-noise understanding and that selective attention is an important ability supporting speech-in-noise understanding in multi-talker scenes.
Analysis of Selection Methods to Develop Novel Phage Therapy Cocktails Against Antimicrobial Resistant Clinical Isolates of Bacteria

Antimicrobial resistance (AMR) is a major problem globally. The main bacterial organisms associated with urinary tract infection (UTI) associated sepsis are E. coli and Klebsiella along with Enterobacter species. These all have AMR strains known as ESBL (Extended Spectrum Beta-Lactamase), which are featured on the WHO priority pathogens list as ‘critical’ for research. Bacteriophages (phages) as viruses that can infect and kill bacteria, could provide an effective tool to tackle these AMR strains. There is currently no ‘gold standard’ for developing a phage cocktail. Here we describe a novel approach to develop an effective phage cocktail against a set of ESBL-producing E. coli and Klebsiella largely isolated from patients in UK hospitals. By comparing different measures of phage efficacy, we show which are the most robust, and suggest an efficient screening cascade that could be used to develop phage cocktails to target other AMR bacterial species. A target panel of 38 ESBL-producing clinical strains isolated from urine samples was collated and used to test phage efficacy. After an initial screening of 68 phages, six were identified and tested against these 38 strains to determine their clinical coverage and killing efficiency. To achieve this, we assessed four different methods to assess phage virulence across these bacterial isolates. These were the Direct Spot Test (DST), the Efficiency of Plating (EOP) assay, the planktonic killing assay and the biofilm assay. The final ESBL cocktail of six phages could effectively kill 23/38 strains (61%) for Klebsiella 13/19 (68%) and for E. coli 10/19 (53%) based on the planktonic killing assay data. The ESBL E. coli collection had six isolates from the prevalent UTI-associated ST131 sequence type, five of which were targeted effectively by the final cocktail. Of the four methods used to assess phage virulence, the data suggests that planktonic killing assays are as effective as the much more time-consuming EOPs and data for the two assays correlates well. This suggests that planktonic killing is a good proxy to determine which phages should be used in a cocktail. This assay when combined with the virulence index also allows ‘phage synergy’ to inform cocktail design.
Wild bee (Apiformes) communities in contrasting habitats within agricultural and wooded landscapes: implications for conservation management

Semi‐natural habitats are characterized by a high diversity of wildlife. However, other areas, e.g. old fields, can also play an important role in biodiversity conservation. We assessed the species richness, abundance, and diversity of wild bees (Apiformes), including species of various functional groups in two contrasting and differently managed landscape types. For this study, we selected 15 xerothermic or sandy grasslands or extensively managed fresh meadows located in agricultural landscapes as well as 15 old fields located in wooded landscapes. The study sites differed in area, stage of succession, and management regime. We did not detect any significant differences in total species richness, abundance, and diversity of Apiformes between the two landscape types, which suggests that both semi‐natural habitats and old fields are highly attractive to bees. The two habitat types, however, differed in species composition and proportions of functional groups. We found that in wooded landscapes, eusocial, hive‐nesting, and large‐sized species increased in abundance. The collected information on the preferences of Apiformes in respect of various habitats and landscapes makes it possible to protect and restore valuable habitats through the implementation of suitable methods of management, both locally and on the scale of landscapes.
Organizational stress in social work : a cross-cultural study

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