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@@ -11,277 +11,327 @@ base_model: thenlper/gte-base
11
  widget:
12
  - source_sentence: Molecular phylogenetic resolution of the mega-diverse clade Apoditrysia
13
  sentences:
14
- - In a previous study of higher-level arthropod phylogeny, analyses of nucleotide
15
- sequences from 62 protein-coding nuclear genes for 80 panarthopod species yielded
16
- significantly higher bootstrap support for selected nodes than did amino acids.
17
- This study investigates the cause of that discrepancy. The hypothesis is tested
18
- that failure to distinguish the serine residues encoded by two disjunct clusters
19
- of codons (TCN, AGY) in amino acid analyses leads to this discrepancy. In one
20
- test, the two clusters of serine codons (Ser1, Ser2) are conceptually translated
21
- as separate amino acids. Analysis of the resulting 21-amino-acid data matrix shows
22
- striking increases in bootstrap support, in some cases matching that in nucleotide
23
- analyses. In a second approach, nucleotide and 20-amino-acid data sets are artificially
24
- altered through targeted deletions, modifications, and replacements, revealing
25
- the pivotal contributions of distinct Ser1 and Ser2 codons. We confirm that previous
26
- methods of coding nonsynonymous nucleotide change are robust and computationally
27
- efficient by introducing two new degeneracy coding methods. We demonstrate for
28
- degeneracy coding that neither compositional heterogeneity at the level of nucleotides
29
- nor codon usage bias between Ser1 and Ser2 clusters of codons (or their separately
30
- coded amino acids) is a major source of non-phylogenetic signal. The incongruity
31
- in support between amino-acid and nucleotide analyses of the forementioned arthropod
32
- data set is resolved by showing that "standard" 20-amino-acid analyses yield lower
33
- node support specifically when serine provides crucial signal. Separate coding
34
- of Ser1 and Ser2 residues yields support commensurate with that found by degenerated
35
- nucleotides, without introducing phylogenetic artifacts. While exclusion of all
36
- serine data leads to reduced support for serine-sensitive nodes, these nodes are
37
- still recovered in the ML topology, indicating that the enhanced signal from Ser1
38
- and Ser2 is not qualitatively different from that of the other amino acids.
39
- - 'Recent molecular phylogenetic studies of the insect order Lepidoptera have robustly
40
- resolved family-level divergences within most superfamilies, and most divergences
41
- among the relatively species-poor early-arising superfamilies. In sharp contrast,
42
- relationships among the superfamilies of more advanced moths and butterflies that
43
- comprise the mega-diverse clade Apoditrysia (ca. 145,000 spp.) remain mostly poorly
44
- supported. This uncertainty, in turn, limits our ability to discern the origins,
45
- ages and evolutionary consequences of traits hypothesized to promote the spectacular
46
- diversification of Apoditrysia. Low support along the apoditrysian "backbone"
47
- probably reflects rapid diversification. If so, it may be feasible to strengthen
48
- resolution by radically increasing the gene sample, but case studies have been
49
- few. We explored the potential of next-generation sequencing to conclusively resolve
50
- apoditrysian relationships. We used transcriptome RNA-Seq to generate 1579 putatively
51
- orthologous gene sequences across a broad sample of 40 apoditrysians plus four
52
- outgroups, to which we added two taxa from previously published data. Phylogenetic
53
- analysis of a 46-taxon, 741-gene matrix, resulting from a strict filter that eliminated
54
- ortholog groups containing any apparent paralogs, yielded dramatic overall increase
55
- in bootstrap support for deeper nodes within Apoditrysia as compared to results
56
- from previous and concurrent 19-gene analyses. High support was restricted mainly
57
- to the huge subclade Obtectomera broadly defined, in which 11 of 12 nodes subtending
58
- multiple superfamilies had bootstrap support of 100%. The strongly supported nodes
59
- showed little conflict with groupings from previous studies, and were little affected
60
- by changes in taxon sampling, suggesting that they reflect true signal rather
61
- than artifacts of massive gene sampling. In contrast, strong support was seen
62
- at only 2 of 11 deeper nodes among the "lower", non-obtectomeran apoditrysians.
63
- These represent a much harder phylogenetic problem, for which one path to resolution
64
- might include further increase in gene sampling, together with improved orthology
65
- assignments. '
66
- - 'One of the major challenges in cell implantation therapies is to promote integration
67
- of the microcirculation between the implanted cells and the host. We used adipose-derived
68
- stromal vascular fraction (SVF) cells to vascularize a human liver cell (HepG2)
69
- implant. We hypothesized that the SVF cells would form a functional microcirculation
70
- via vascular assembly and inosculation with the host vasculature. Initially, we
71
- assessed the extent and character of neovasculatures formed by freshly isolated
72
- and cultured SVF cells and found that freshly isolated cells have a higher vascularization
73
- potential. Generation of a 3D implant containing fresh SVF and HepG2 cells formed
74
- a tissue in which HepG2 cells were entwined with a network of microvessels. Implanted
75
- HepG2 cells sequestered labeled LDL delivered by systemic intravascular injection
76
- only in SVF-vascularized implants demonstrating that SVF cell-derived vasculatures
77
- can effectively integrate with host vessels and interface with parenchymal cells
78
- to form a functional tissue mimic. '
 
 
 
 
 
 
 
 
 
 
 
79
  - source_sentence: Exosomes as drug delivery systems for gastrointestinal cancers
80
  sentences:
81
- - Gastrointestinal cancer is one of the most common malignancies with relatively
82
- high morbidity and mortality. Exosomes are nanosized extracellular vesicles derived
83
- from most cells and widely distributed in body fluids. They are natural endogenous
84
- nanocarriers with low immunogenicity, high biocompatibility, and natural targeting,
85
- and can transport lipids, proteins, DNA, and RNA. Exosomes contain DNA, RNA, proteins,
86
- lipids, and other bioactive components, which can play a role in information transmission
87
- and regulation of cellular physiological and pathological processes during the
88
- progression of gastrointestinal cancer. In this paper, the role of exosomes in
89
- gastrointestinal cancers is briefly reviewed, with emphasis on the application
90
- of exosomes as drug delivery systems for gastrointestinal cancers. Finally, the
91
- challenges faced by exosome-based drug delivery systems are discussed.
92
- - Background In the myocardium, pericytes are often confused with other interstitial
93
- cell types, such as fibroblasts. The lack of well-characterized and specific tools
94
- for identification, lineage tracing, and conditional targeting of myocardial pericytes
95
- has hampered studies on their role in heart disease. In the current study, we
96
- characterize and validate specific and reliable strategies for labeling and targeting
97
- of cardiac pericytes. Methods and Results Using the neuron-glial antigen 2 (NG2)
98
- - Exosomes are small extracellular vesicles with diameters of 30-150 nm. In both
99
- physiological and pathological conditions, nearly all types of cells can release
100
- exosomes, which play important roles in cell communication and epigenetic regulation
101
- by transporting crucial protein and genetic materials such as miRNA, mRNA, and
102
- DNA. Consequently, exosome-based disease diagnosis and therapeutic methods have
103
- been intensively investigated. However, as in any natural science field, the in-depth
104
- investigation of exosomes relies heavily on technological advances. Historically,
105
- the two main technical hindrances that have restricted the basic and applied researches
106
- of exosomes include, first, how to simplify the extraction and improve the yield
107
- of exosomes and, second, how to effectively distinguish exosomes from other extracellular
108
- vesicles, especially functional microvesicles. Over the past few decades, although
109
- a standardized exosome isolation method has still not become available, a number
110
- of techniques have been established through exploration of the biochemical and
111
- physicochemical features of exosomes. In this work, by comprehensively analyzing
112
- the progresses in exosome separation strategies, we provide a panoramic view of
113
- current exosome isolation techniques, providing perspectives toward the development
114
- of novel approaches for high-efficient exosome isolation from various types of
115
- biological matrices. In addition, from the perspective of exosome-based diagnosis
116
- and therapeutics, we emphasize the issue of quantitative exosome and microvesicle
117
- separation.
118
- - source_sentence: Comparison of pesticide active substances in conventional agriculture
119
- and organic agriculture in Europe
 
 
 
 
 
 
 
 
 
120
  sentences:
121
- - Total concentrations of metals in soil are poor predictors of toxicity. In the
122
- last decade, considerable effort has been made to demonstrate how metal toxicity
123
- is affected by the abiotic properties of soil. Here this information is collated
124
- and shows how these data have been used in the European Union for defining predicted-no-effect
125
- concentrations (PNECs) of Cd, Cu, Co, Ni, Pb, and Zn in soil. Bioavailability
126
- models have been calibrated using data from more than 500 new chronic toxicity
127
- tests in soils amended with soluble metal salts, in experimentally aged soils,
128
- and in field-contaminated soils. In general, soil pH was a good predictor of metal
129
- solubility but a poor predictor of metal toxicity across soils. Toxicity thresholds
130
- based on the free metal ion activity were generally more variable than those expressed
131
- on total soil metal, which can be explained, but not predicted, using the concept
132
- of the biotic ligand model. The toxicity thresholds based on total soil metal
133
- concentrations rise almost proportionally to the effective cation exchange capacity
134
- of soil. Total soil metal concentrations yielding 10% inhibition in freshly amended
135
- soils were up to 100-fold smaller (median 3.4-fold, n = 110 comparative tests)
136
- than those in corresponding aged soils or field-contaminated soils. The change
137
- in isotopically exchangeable metal in soil proved to be a conservative estimate
138
- of the change in toxicity upon aging. The PNEC values for specific soil types
139
- were calculated using this information. The corrections for aging and for modifying
140
- effects of soil properties in metal-salt-amended soils are shown to be the main
141
- factors by which PNEC values rise above the natural background range.
142
- - There is much debate about whether the (mostly synthetic) pesticide active substances
143
- (AS) in conventional agriculture have different non-target effects than the natural
144
- AS in organic agriculture. We evaluated the official EU pesticide database to
145
- compare 256 AS that may only be used on conventional farmland with 134 AS that
146
- are permitted on organic farmland. As a benchmark, we used (i) the hazard classifications
147
- of the Globally Harmonized System (GHS), and (ii) the dietary and occupational
148
- health-based guidance values, which were established in the authorization procedure.
149
- Our comparison showed that 55% of the AS used only in conventional agriculture
150
- contained health or environmental hazard statements, but only 3% did of the AS
151
- authorized for organic agriculture. Warnings about possible harm to the unborn
152
- child, suspected carcinogenicity, or acute lethal effects were found in 16% of
153
- the AS used in conventional agriculture, but none were found in organic agriculture.
154
- Furthermore, the establishment of health-based guidance values for dietary and
155
- non-dietary exposures were relevant by the European authorities for 93% of conventional
156
- AS, but only for 7% of organic AS. We, therefore, encourage policies and strategies
157
- to reduce the use and risk of pesticides, and to strengthen organic farming in
158
- order to protect biodiversity and maintain food security.
159
- - Herpes simplex virus 1 (HSV-1) encodes Us3 protein kinase, which is critical for
160
- viral pathogenicity in both mouse peripheral sites (e.g., eyes and vaginas) and
161
- in the central nervous systems (CNS) of mice after intracranial and peripheral
162
- inoculations, respectively. Whereas some Us3 substrates involved in Us3 pathogenicity
163
- in peripheral sites have been reported, those involved in Us3 pathogenicity in
164
- the CNS remain to be identified. We recently reported that Us3 phosphorylated
165
- HSV-1 dUTPase (vdUTPase) at serine 187 (Ser-187) in infected cells, and this phosphorylation
166
- promoted viral replication by regulating optimal enzymatic activity of vdUTPase.
167
- In the present study, we show that the replacement of vdUTPase Ser-187 by alanine
168
- (S187A) significantly reduced viral replication and virulence in the CNS of mice
169
- following intracranial inoculation and that the phosphomimetic substitution at
170
- vdUTPase Ser-187 in part restored the wild-type viral replication and virulence.
171
- Interestingly, the S187A mutation in vdUTPase had no effect on viral replication
172
- and pathogenic effects in the eyes and vaginas of mice after ocular and vaginal
173
- inoculation, respectively. Similarly, the enzyme-dead mutation in vdUTPase significantly
174
- reduced viral replication and virulence in the CNS of mice after intracranial
175
- inoculation, whereas the mutation had no effect on viral replication and pathogenic
176
- effects in the eyes and vaginas of mice after ocular and vaginal inoculation,
177
- respectively. These observations suggested that vdUTPase was one of the Us3 substrates
178
- responsible for Us3 pathogenicity in the CNS and that the CNS-specific virulence
179
- of HSV-1 involved strict regulation of vdUTPase activity by Us3 phosphorylation.
180
- - source_sentence: Load-dependent detachment and reattachment kinetics of kinesin-1,
181
- -2 and 3 motors
 
 
 
 
 
 
 
 
 
 
 
 
182
  sentences:
183
- - Bidirectional cargo transport by kinesin and dynein is essential for cell viability
184
- and defects are linked to neurodegenerative diseases. Computational modeling suggests
185
- that the load-dependent off-rate is the strongest determinant of which motor 'wins'
186
- a kinesin-dynein tug-of-war, and optical tweezer experiments find that the load-dependent
187
- detachment sensitivity of transport kinesins is kinesin-3 > kinesin-2 > kinesin-1.
188
- However, in reconstituted kinesin-dynein pairs vitro, all three kinesin families
189
- compete nearly equally well against dynein. Modeling and experiments have confirmed
190
- that vertical forces inherent to the large trapping beads enhance kinesin-1 dissociation
191
- rates. In vivo, vertical forces are expected to range from negligible to dominant,
192
- depending on cargo and microtubule geometries. To investigate the detachment and
193
- reattachment kinetics of kinesin-1, 2 and 3 motors against loads oriented parallel
194
- to the microtubule, we created a DNA tensiometer comprising a DNA entropic spring
195
- attached to the microtubule on one end and a motor on the other. Kinesin dissociation
196
- rates at stall were slower than detachment rates during unloaded runs, and the
197
- complex reattachment kinetics were consistent with a weakly-bound 'slip' state
198
- preceding detachment. Kinesin-3 behaviors under load suggested that long KIF1A
199
- run lengths result from the concatenation of multiple short runs connected by
200
- diffusive episodes. Stochastic simulations were able to recapitulate the load-dependent
201
- detachment and reattachment kinetics for all three motors and provide direct comparison
202
- of key transition rates between families. These results provide insight into how
203
- kinesin-1, -2 and -3 families transport cargo in complex cellular geometries and
204
- compete against dynein during bidirectional transport.
205
- - 'AP-1 and AP-2 adaptor protein (AP) complexes mediate clathrin-dependent trafficking
206
- at the trans-Golgi network (TGN) and the plasma membrane, respectively. Whereas
207
- AP-1 is required for trafficking to plasma membrane and vacuoles, AP-2 mediates
208
- endocytosis. These AP complexes consist of four subunits (adaptins): two large
209
- subunits (β1 and γ for AP-1 and β2 and α for AP-2), a medium subunit μ, and a
210
- small subunit σ. In general, adaptins are unique to each AP complex, with the
211
- exception of β subunits that are shared by AP-1 and AP-2 in some invertebrates.
212
- Here, we show that the two putative Arabidopsis thaliana AP1/2β adaptins co-assemble
213
- with both AP-1 and AP-2 subunits and regulate exocytosis and endocytosis in root
214
- cells, consistent with their dual localization at the TGN and plasma membrane.
215
- Deletion of both β adaptins is lethal in plants. We identified a critical role
216
- of β adaptins in pollen wall formation and reproduction, involving the regulation
217
- of membrane trafficking in the tapetum and pollen germination. In tapetal cells,
218
- β adaptins localize almost exclusively to the TGN and mediate exocytosis of the
219
- plasma membrane transporters such as ATP-binding cassette (ABC)G9 and ABCG16.
220
- This study highlights the essential role of AP1/2β adaptins in plants and their
221
- specialized roles in specific cell types.'
222
- - A single kinesin molecule can move "processively" along a microtubule for more
223
- than 1 micrometer before detaching from it. The prevailing explanation for this
224
- processive movement is the "walking model," which envisions that each of two motor
225
- domains (heads) of the kinesin molecule binds coordinately to the microtubule.
226
- This implies that each kinesin molecule must have two heads to "walk" and that
227
- a single-headed kinesin could not move processively. Here, a motor-domain construct
228
- of KIF1A, a single-headed kinesin superfamily protein, was shown to move processively
229
- along the microtubule for more than 1 micrometer. The movement along the microtubules
 
 
 
 
 
 
 
 
230
  was stochastic and fitted a biased Brownian-movement model.
231
- - source_sentence: Phylogenetic analysis of mitochondrial genes in Macquarie perch
232
- from three river basins
 
233
  sentences:
234
- - Sedentary behavior is an emerging risk factor for cardiovascular disease (CVD)
235
- and may be particularly relevant to the cardiovascular health of older adults.
236
- This scoping review describes the existing literature examining the prevalence
237
- of sedentary time in older adults with CVD and the association of sedentary behavior
238
- with cardiovascular risk in older adults. We found that older adults with CVD
239
- spend >75 % of their waking day sedentary, and that sedentary time is higher among
240
- older adults with CVD than among older adults without CVD. High sedentary behavior
241
- is consistently associated with worse cardiac lipid profiles and increased cardiac
242
- risk scores in older adults; the associations of sedentary behavior with blood
243
- pressure, CVD incidence, and CVD-related mortality among older adults are less
244
- clear. Future research with larger sample sizes using validated methods to measure
245
- sedentary behavior are needed to clarify the association between sedentary behavior
 
 
246
  and cardiovascular outcomes in older adults.
247
- - An improved Bayesian method is presented for estimating phylogenetic trees using
248
- DNA sequence data. The birth-death process with species sampling is used to specify
249
- the prior distribution of phylogenies and ancestral speciation times, and the
250
- posterior probabilities of phylogenies are used to estimate the maximum posterior
251
- probability (MAP) tree. Monte Carlo integration is used to integrate over the
252
- ancestral speciation times for particular trees. A Markov Chain Monte Carlo method
253
- is used to generate the set of trees with the highest posterior probabilities.
254
- Methods are described for an empirical Bayesian analysis, in which estimates of
255
- the speciation and extinction rates are used in calculating the posterior probabilities,
256
- and a hierarchical Bayesian analysis, in which these parameters are removed from
257
- the model by an additional integration. The Markov Chain Monte Carlo method avoids
258
- the requirement of our earlier method for calculating MAP trees to sum over all
259
- possible topologies (which limited the number of taxa in an analysis to about
260
- five). The methods are applied to analyze DNA sequences for nine species of primates,
261
- and the MAP tree, which is identical to a maximum-likelihood estimate of topology,
262
- has a probability of approximately 95%.
263
- - 'Genetic variation in mitochondrial genes could underlie metabolic adaptations
264
- because mitochondrially encoded proteins are directly involved in a pathway supplying
265
- energy to metabolism. Macquarie perch from river basins exposed to different climates
266
- differ in size and growth rate, suggesting potential presence of adaptive metabolic
267
- differences. We used complete mitochondrial genome sequences to build a phylogeny,
268
- estimate lineage divergence times and identify signatures of purifying and positive
269
- selection acting on mitochondrial genes for 25 Macquarie perch from three basins:
270
- Murray-Darling Basin (MDB), Hawkesbury-Nepean Basin (HNB) and Shoalhaven Basin
271
- (SB). Phylogenetic analysis resolved basin-level clades, supporting incipient
272
- speciation previously inferred from differentiation in allozymes, microsatellites
273
- and mitochondrial control region. The estimated time of lineage divergence suggested
274
- an early- to mid-Pleistocene split between SB and the common ancestor of HNB+MDB,
275
- followed by mid-to-late Pleistocene splitting between HNB and MDB. These divergence
276
- estimates are more recent than previous ones. Our analyses suggested that evolutionary
277
- drivers differed between inland MDB and coastal HNB. In the cooler and more climatically
278
- variable MDB, mitogenomes evolved under strong purifying selection, whereas in
279
- the warmer and more climatically stable HNB, purifying selection was relaxed.
280
- Evidence for relaxed selection in the HNB includes elevated transfer RNA and 16S
281
- ribosomal RNA polymorphism, presence of potentially mildly deleterious mutations
282
- and a codon (ATP6'
 
 
 
 
 
 
283
  pipeline_tag: sentence-similarity
284
  library_name: sentence-transformers
 
285
  ---
286
 
287
  # SentenceTransformer based on thenlper/gte-base
 
11
  widget:
12
  - source_sentence: Molecular phylogenetic resolution of the mega-diverse clade Apoditrysia
13
  sentences:
14
+ - >-
15
+ In a previous study of higher-level arthropod phylogeny, analyses of
16
+ nucleotide sequences from 62 protein-coding nuclear genes for 80 panarthopod
17
+ species yielded significantly higher bootstrap support for selected nodes
18
+ than did amino acids. This study investigates the cause of that discrepancy.
19
+ The hypothesis is tested that failure to distinguish the serine residues
20
+ encoded by two disjunct clusters of codons (TCN, AGY) in amino acid analyses
21
+ leads to this discrepancy. In one test, the two clusters of serine codons
22
+ (Ser1, Ser2) are conceptually translated as separate amino acids. Analysis
23
+ of the resulting 21-amino-acid data matrix shows striking increases in
24
+ bootstrap support, in some cases matching that in nucleotide analyses. In a
25
+ second approach, nucleotide and 20-amino-acid data sets are artificially
26
+ altered through targeted deletions, modifications, and replacements,
27
+ revealing the pivotal contributions of distinct Ser1 and Ser2 codons. We
28
+ confirm that previous methods of coding nonsynonymous nucleotide change are
29
+ robust and computationally efficient by introducing two new degeneracy
30
+ coding methods. We demonstrate for degeneracy coding that neither
31
+ compositional heterogeneity at the level of nucleotides nor codon usage bias
32
+ between Ser1 and Ser2 clusters of codons (or their separately coded amino
33
+ acids) is a major source of non-phylogenetic signal. The incongruity in
34
+ support between amino-acid and nucleotide analyses of the forementioned
35
+ arthropod data set is resolved by showing that "standard" 20-amino-acid
36
+ analyses yield lower node support specifically when serine provides crucial
37
+ signal. Separate coding of Ser1 and Ser2 residues yields support
38
+ commensurate with that found by degenerated nucleotides, without introducing
39
+ phylogenetic artifacts. While exclusion of all serine data leads to reduced
40
+ support for serine-sensitive nodes, these nodes are still recovered in the
41
+ ML topology, indicating that the enhanced signal from Ser1 and Ser2 is not
42
+ qualitatively different from that of the other amino acids.
43
+ - >-
44
+ Recent molecular phylogenetic studies of the insect order Lepidoptera have
45
+ robustly resolved family-level divergences within most superfamilies, and
46
+ most divergences among the relatively species-poor early-arising
47
+ superfamilies. In sharp contrast, relationships among the superfamilies of
48
+ more advanced moths and butterflies that comprise the mega-diverse clade
49
+ Apoditrysia (ca. 145,000 spp.) remain mostly poorly supported. This
50
+ uncertainty, in turn, limits our ability to discern the origins, ages and
51
+ evolutionary consequences of traits hypothesized to promote the spectacular
52
+ diversification of Apoditrysia. Low support along the apoditrysian
53
+ "backbone" probably reflects rapid diversification. If so, it may be
54
+ feasible to strengthen resolution by radically increasing the gene sample,
55
+ but case studies have been few. We explored the potential of next-generation
56
+ sequencing to conclusively resolve apoditrysian relationships. We used
57
+ transcriptome RNA-Seq to generate 1579 putatively orthologous gene sequences
58
+ across a broad sample of 40 apoditrysians plus four outgroups, to which we
59
+ added two taxa from previously published data. Phylogenetic analysis of a
60
+ 46-taxon, 741-gene matrix, resulting from a strict filter that eliminated
61
+ ortholog groups containing any apparent paralogs, yielded dramatic overall
62
+ increase in bootstrap support for deeper nodes within Apoditrysia as
63
+ compared to results from previous and concurrent 19-gene analyses. High
64
+ support was restricted mainly to the huge subclade Obtectomera broadly
65
+ defined, in which 11 of 12 nodes subtending multiple superfamilies had
66
+ bootstrap support of 100%. The strongly supported nodes showed little
67
+ conflict with groupings from previous studies, and were little affected by
68
+ changes in taxon sampling, suggesting that they reflect true signal rather
69
+ than artifacts of massive gene sampling. In contrast, strong support was
70
+ seen at only 2 of 11 deeper nodes among the "lower", non-obtectomeran
71
+ apoditrysians. These represent a much harder phylogenetic problem, for which
72
+ one path to resolution might include further increase in gene sampling,
73
+ together with improved orthology assignments.
74
+ - >-
75
+ One of the major challenges in cell implantation therapies is to promote
76
+ integration of the microcirculation between the implanted cells and the
77
+ host. We used adipose-derived stromal vascular fraction (SVF) cells to
78
+ vascularize a human liver cell (HepG2) implant. We hypothesized that the SVF
79
+ cells would form a functional microcirculation via vascular assembly and
80
+ inosculation with the host vasculature. Initially, we assessed the extent
81
+ and character of neovasculatures formed by freshly isolated and cultured SVF
82
+ cells and found that freshly isolated cells have a higher vascularization
83
+ potential. Generation of a 3D implant containing fresh SVF and HepG2 cells
84
+ formed a tissue in which HepG2 cells were entwined with a network of
85
+ microvessels. Implanted HepG2 cells sequestered labeled LDL delivered by
86
+ systemic intravascular injection only in SVF-vascularized implants
87
+ demonstrating that SVF cell-derived vasculatures can effectively integrate
88
+ with host vessels and interface with parenchymal cells to form a functional
89
+ tissue mimic.
90
  - source_sentence: Exosomes as drug delivery systems for gastrointestinal cancers
91
  sentences:
92
+ - >-
93
+ Gastrointestinal cancer is one of the most common malignancies with
94
+ relatively high morbidity and mortality. Exosomes are nanosized
95
+ extracellular vesicles derived from most cells and widely distributed in
96
+ body fluids. They are natural endogenous nanocarriers with low
97
+ immunogenicity, high biocompatibility, and natural targeting, and can
98
+ transport lipids, proteins, DNA, and RNA. Exosomes contain DNA, RNA,
99
+ proteins, lipids, and other bioactive components, which can play a role in
100
+ information transmission and regulation of cellular physiological and
101
+ pathological processes during the progression of gastrointestinal cancer. In
102
+ this paper, the role of exosomes in gastrointestinal cancers is briefly
103
+ reviewed, with emphasis on the application of exosomes as drug delivery
104
+ systems for gastrointestinal cancers. Finally, the challenges faced by
105
+ exosome-based drug delivery systems are discussed.
106
+ - >-
107
+ Background In the myocardium, pericytes are often confused with other
108
+ interstitial cell types, such as fibroblasts. The lack of well-characterized
109
+ and specific tools for identification, lineage tracing, and conditional
110
+ targeting of myocardial pericytes has hampered studies on their role in
111
+ heart disease. In the current study, we characterize and validate specific
112
+ and reliable strategies for labeling and targeting of cardiac pericytes.
113
+ Methods and Results Using the neuron-glial antigen 2 (NG2)
114
+ - >-
115
+ Exosomes are small extracellular vesicles with diameters of 30-150 nm. In
116
+ both physiological and pathological conditions, nearly all types of cells
117
+ can release exosomes, which play important roles in cell communication and
118
+ epigenetic regulation by transporting crucial protein and genetic materials
119
+ such as miRNA, mRNA, and DNA. Consequently, exosome-based disease diagnosis
120
+ and therapeutic methods have been intensively investigated. However, as in
121
+ any natural science field, the in-depth investigation of exosomes relies
122
+ heavily on technological advances. Historically, the two main technical
123
+ hindrances that have restricted the basic and applied researches of exosomes
124
+ include, first, how to simplify the extraction and improve the yield of
125
+ exosomes and, second, how to effectively distinguish exosomes from other
126
+ extracellular vesicles, especially functional microvesicles. Over the past
127
+ few decades, although a standardized exosome isolation method has still not
128
+ become available, a number of techniques have been established through
129
+ exploration of the biochemical and physicochemical features of exosomes. In
130
+ this work, by comprehensively analyzing the progresses in exosome separation
131
+ strategies, we provide a panoramic view of current exosome isolation
132
+ techniques, providing perspectives toward the development of novel
133
+ approaches for high-efficient exosome isolation from various types of
134
+ biological matrices. In addition, from the perspective of exosome-based
135
+ diagnosis and therapeutics, we emphasize the issue of quantitative exosome
136
+ and microvesicle separation.
137
+ - source_sentence: >-
138
+ Comparison of pesticide active substances in conventional agriculture and
139
+ organic agriculture in Europe
140
  sentences:
141
+ - >-
142
+ Total concentrations of metals in soil are poor predictors of toxicity. In
143
+ the last decade, considerable effort has been made to demonstrate how metal
144
+ toxicity is affected by the abiotic properties of soil. Here this
145
+ information is collated and shows how these data have been used in the
146
+ European Union for defining predicted-no-effect concentrations (PNECs) of
147
+ Cd, Cu, Co, Ni, Pb, and Zn in soil. Bioavailability models have been
148
+ calibrated using data from more than 500 new chronic toxicity tests in soils
149
+ amended with soluble metal salts, in experimentally aged soils, and in
150
+ field-contaminated soils. In general, soil pH was a good predictor of metal
151
+ solubility but a poor predictor of metal toxicity across soils. Toxicity
152
+ thresholds based on the free metal ion activity were generally more variable
153
+ than those expressed on total soil metal, which can be explained, but not
154
+ predicted, using the concept of the biotic ligand model. The toxicity
155
+ thresholds based on total soil metal concentrations rise almost
156
+ proportionally to the effective cation exchange capacity of soil. Total soil
157
+ metal concentrations yielding 10% inhibition in freshly amended soils were
158
+ up to 100-fold smaller (median 3.4-fold, n = 110 comparative tests) than
159
+ those in corresponding aged soils or field-contaminated soils. The change in
160
+ isotopically exchangeable metal in soil proved to be a conservative estimate
161
+ of the change in toxicity upon aging. The PNEC values for specific soil
162
+ types were calculated using this information. The corrections for aging and
163
+ for modifying effects of soil properties in metal-salt-amended soils are
164
+ shown to be the main factors by which PNEC values rise above the natural
165
+ background range.
166
+ - >-
167
+ There is much debate about whether the (mostly synthetic) pesticide active
168
+ substances (AS) in conventional agriculture have different non-target
169
+ effects than the natural AS in organic agriculture. We evaluated the
170
+ official EU pesticide database to compare 256 AS that may only be used on
171
+ conventional farmland with 134 AS that are permitted on organic farmland. As
172
+ a benchmark, we used (i) the hazard classifications of the Globally
173
+ Harmonized System (GHS), and (ii) the dietary and occupational health-based
174
+ guidance values, which were established in the authorization procedure. Our
175
+ comparison showed that 55% of the AS used only in conventional agriculture
176
+ contained health or environmental hazard statements, but only 3% did of the
177
+ AS authorized for organic agriculture. Warnings about possible harm to the
178
+ unborn child, suspected carcinogenicity, or acute lethal effects were found
179
+ in 16% of the AS used in conventional agriculture, but none were found in
180
+ organic agriculture. Furthermore, the establishment of health-based guidance
181
+ values for dietary and non-dietary exposures were relevant by the European
182
+ authorities for 93% of conventional AS, but only for 7% of organic AS. We,
183
+ therefore, encourage policies and strategies to reduce the use and risk of
184
+ pesticides, and to strengthen organic farming in order to protect
185
+ biodiversity and maintain food security.
186
+ - >-
187
+ Herpes simplex virus 1 (HSV-1) encodes Us3 protein kinase, which is critical
188
+ for viral pathogenicity in both mouse peripheral sites (e.g., eyes and
189
+ vaginas) and in the central nervous systems (CNS) of mice after intracranial
190
+ and peripheral inoculations, respectively. Whereas some Us3 substrates
191
+ involved in Us3 pathogenicity in peripheral sites have been reported, those
192
+ involved in Us3 pathogenicity in the CNS remain to be identified. We
193
+ recently reported that Us3 phosphorylated HSV-1 dUTPase (vdUTPase) at serine
194
+ 187 (Ser-187) in infected cells, and this phosphorylation promoted viral
195
+ replication by regulating optimal enzymatic activity of vdUTPase. In the
196
+ present study, we show that the replacement of vdUTPase Ser-187 by alanine
197
+ (S187A) significantly reduced viral replication and virulence in the CNS of
198
+ mice following intracranial inoculation and that the phosphomimetic
199
+ substitution at vdUTPase Ser-187 in part restored the wild-type viral
200
+ replication and virulence. Interestingly, the S187A mutation in vdUTPase had
201
+ no effect on viral replication and pathogenic effects in the eyes and
202
+ vaginas of mice after ocular and vaginal inoculation, respectively.
203
+ Similarly, the enzyme-dead mutation in vdUTPase significantly reduced viral
204
+ replication and virulence in the CNS of mice after intracranial inoculation,
205
+ whereas the mutation had no effect on viral replication and pathogenic
206
+ effects in the eyes and vaginas of mice after ocular and vaginal
207
+ inoculation, respectively. These observations suggested that vdUTPase was
208
+ one of the Us3 substrates responsible for Us3 pathogenicity in the CNS and
209
+ that the CNS-specific virulence of HSV-1 involved strict regulation of
210
+ vdUTPase activity by Us3 phosphorylation.
211
+ - source_sentence: >-
212
+ Load-dependent detachment and reattachment kinetics of kinesin-1, -2 and 3
213
+ motors
214
  sentences:
215
+ - >-
216
+ Bidirectional cargo transport by kinesin and dynein is essential for cell
217
+ viability and defects are linked to neurodegenerative diseases.
218
+ Computational modeling suggests that the load-dependent off-rate is the
219
+ strongest determinant of which motor 'wins' a kinesin-dynein tug-of-war, and
220
+ optical tweezer experiments find that the load-dependent detachment
221
+ sensitivity of transport kinesins is kinesin-3 > kinesin-2 > kinesin-1.
222
+ However, in reconstituted kinesin-dynein pairs vitro, all three kinesin
223
+ families compete nearly equally well against dynein. Modeling and
224
+ experiments have confirmed that vertical forces inherent to the large
225
+ trapping beads enhance kinesin-1 dissociation rates. In vivo, vertical
226
+ forces are expected to range from negligible to dominant, depending on cargo
227
+ and microtubule geometries. To investigate the detachment and reattachment
228
+ kinetics of kinesin-1, 2 and 3 motors against loads oriented parallel to the
229
+ microtubule, we created a DNA tensiometer comprising a DNA entropic spring
230
+ attached to the microtubule on one end and a motor on the other. Kinesin
231
+ dissociation rates at stall were slower than detachment rates during
232
+ unloaded runs, and the complex reattachment kinetics were consistent with a
233
+ weakly-bound 'slip' state preceding detachment. Kinesin-3 behaviors under
234
+ load suggested that long KIF1A run lengths result from the concatenation of
235
+ multiple short runs connected by diffusive episodes. Stochastic simulations
236
+ were able to recapitulate the load-dependent detachment and reattachment
237
+ kinetics for all three motors and provide direct comparison of key
238
+ transition rates between families. These results provide insight into how
239
+ kinesin-1, -2 and -3 families transport cargo in complex cellular geometries
240
+ and compete against dynein during bidirectional transport.
241
+ - >-
242
+ AP-1 and AP-2 adaptor protein (AP) complexes mediate clathrin-dependent
243
+ trafficking at the trans-Golgi network (TGN) and the plasma membrane,
244
+ respectively. Whereas AP-1 is required for trafficking to plasma membrane
245
+ and vacuoles, AP-2 mediates endocytosis. These AP complexes consist of four
246
+ subunits (adaptins): two large subunits (β1 and γ for AP-1 and β2 and α for
247
+ AP-2), a medium subunit μ, and a small subunit σ. In general, adaptins are
248
+ unique to each AP complex, with the exception of β subunits that are shared
249
+ by AP-1 and AP-2 in some invertebrates. Here, we show that the two putative
250
+ Arabidopsis thaliana AP1/2β adaptins co-assemble with both AP-1 and AP-2
251
+ subunits and regulate exocytosis and endocytosis in root cells, consistent
252
+ with their dual localization at the TGN and plasma membrane. Deletion of
253
+ both β adaptins is lethal in plants. We identified a critical role of β
254
+ adaptins in pollen wall formation and reproduction, involving the regulation
255
+ of membrane trafficking in the tapetum and pollen germination. In tapetal
256
+ cells, β adaptins localize almost exclusively to the TGN and mediate
257
+ exocytosis of the plasma membrane transporters such as ATP-binding cassette
258
+ (ABC)G9 and ABCG16. This study highlights the essential role of AP1/2β
259
+ adaptins in plants and their specialized roles in specific cell types.
260
+ - >-
261
+ A single kinesin molecule can move "processively" along a microtubule for
262
+ more than 1 micrometer before detaching from it. The prevailing explanation
263
+ for this processive movement is the "walking model," which envisions that
264
+ each of two motor domains (heads) of the kinesin molecule binds coordinately
265
+ to the microtubule. This implies that each kinesin molecule must have two
266
+ heads to "walk" and that a single-headed kinesin could not move
267
+ processively. Here, a motor-domain construct of KIF1A, a single-headed
268
+ kinesin superfamily protein, was shown to move processively along the
269
+ microtubule for more than 1 micrometer. The movement along the microtubules
270
  was stochastic and fitted a biased Brownian-movement model.
271
+ - source_sentence: >-
272
+ Phylogenetic analysis of mitochondrial genes in Macquarie perch from three
273
+ river basins
274
  sentences:
275
+ - >-
276
+ Sedentary behavior is an emerging risk factor for cardiovascular disease
277
+ (CVD) and may be particularly relevant to the cardiovascular health of older
278
+ adults. This scoping review describes the existing literature examining the
279
+ prevalence of sedentary time in older adults with CVD and the association of
280
+ sedentary behavior with cardiovascular risk in older adults. We found that
281
+ older adults with CVD spend >75 % of their waking day sedentary, and that
282
+ sedentary time is higher among older adults with CVD than among older adults
283
+ without CVD. High sedentary behavior is consistently associated with worse
284
+ cardiac lipid profiles and increased cardiac risk scores in older adults;
285
+ the associations of sedentary behavior with blood pressure, CVD incidence,
286
+ and CVD-related mortality among older adults are less clear. Future research
287
+ with larger sample sizes using validated methods to measure sedentary
288
+ behavior are needed to clarify the association between sedentary behavior
289
  and cardiovascular outcomes in older adults.
290
+ - >-
291
+ An improved Bayesian method is presented for estimating phylogenetic trees
292
+ using DNA sequence data. The birth-death process with species sampling is
293
+ used to specify the prior distribution of phylogenies and ancestral
294
+ speciation times, and the posterior probabilities of phylogenies are used to
295
+ estimate the maximum posterior probability (MAP) tree. Monte Carlo
296
+ integration is used to integrate over the ancestral speciation times for
297
+ particular trees. A Markov Chain Monte Carlo method is used to generate the
298
+ set of trees with the highest posterior probabilities. Methods are described
299
+ for an empirical Bayesian analysis, in which estimates of the speciation and
300
+ extinction rates are used in calculating the posterior probabilities, and a
301
+ hierarchical Bayesian analysis, in which these parameters are removed from
302
+ the model by an additional integration. The Markov Chain Monte Carlo method
303
+ avoids the requirement of our earlier method for calculating MAP trees to
304
+ sum over all possible topologies (which limited the number of taxa in an
305
+ analysis to about five). The methods are applied to analyze DNA sequences
306
+ for nine species of primates, and the MAP tree, which is identical to a
307
+ maximum-likelihood estimate of topology, has a probability of approximately
308
+ 95%.
309
+ - >-
310
+ Genetic variation in mitochondrial genes could underlie metabolic
311
+ adaptations because mitochondrially encoded proteins are directly involved
312
+ in a pathway supplying energy to metabolism. Macquarie perch from river
313
+ basins exposed to different climates differ in size and growth rate,
314
+ suggesting potential presence of adaptive metabolic differences. We used
315
+ complete mitochondrial genome sequences to build a phylogeny, estimate
316
+ lineage divergence times and identify signatures of purifying and positive
317
+ selection acting on mitochondrial genes for 25 Macquarie perch from three
318
+ basins: Murray-Darling Basin (MDB), Hawkesbury-Nepean Basin (HNB) and
319
+ Shoalhaven Basin (SB). Phylogenetic analysis resolved basin-level clades,
320
+ supporting incipient speciation previously inferred from differentiation in
321
+ allozymes, microsatellites and mitochondrial control region. The estimated
322
+ time of lineage divergence suggested an early- to mid-Pleistocene split
323
+ between SB and the common ancestor of HNB+MDB, followed by mid-to-late
324
+ Pleistocene splitting between HNB and MDB. These divergence estimates are
325
+ more recent than previous ones. Our analyses suggested that evolutionary
326
+ drivers differed between inland MDB and coastal HNB. In the cooler and more
327
+ climatically variable MDB, mitogenomes evolved under strong purifying
328
+ selection, whereas in the warmer and more climatically stable HNB, purifying
329
+ selection was relaxed. Evidence for relaxed selection in the HNB includes
330
+ elevated transfer RNA and 16S ribosomal RNA polymorphism, presence of
331
+ potentially mildly deleterious mutations and a codon (ATP6
332
  pipeline_tag: sentence-similarity
333
  library_name: sentence-transformers
334
+ license: mit
335
  ---
336
 
337
  # SentenceTransformer based on thenlper/gte-base