1 racterized detailed mechanistic functions of
two hits.
2 MTSEA(+) modification of the dimer occurs in
two hits.
3 al for identifying combinations of more than
two hits.
4 (58%, n=118), followed by mixed etiologies ("
two-hits") (
18%, n=36) and AD (10%, n=21).
5 Interestingly, a distinct
two-hit activation process has been recently described f
6 y (ALI): LPS-induced inflammatory injury and
two-hit ALI caused by suboptimal mechanical ventilation
7 ce events revealed driver genes with shared "
two-hit"
alterations in the airway field (e.g., TP53, KR
8 The availability of this ras and p53
two-hit animal model system recapitulating HNSCC progres
9 oteins probably retain some function and the
two hits are co-selected to produce an optimal level of
10 gression, leading to selection for more than
two hits at the APC locus.
11 ary models, such as oncogene activation and "
two hits"
at tumor suppressor loci.
12 The '
two hits'
at APC are coselected so as to produce an opti
13 Two hits,
ATA and NF023, obtained in both screens were c
14 We identified
two hits behaving as competitive inhibitors of pathogen
15 ing using an ACKR3 homology model identified
two hits,
C10 (EC(50) 19.1 muM) and C11 (EC(50) = 11.4 m
16 are induced by paracrine factors released by
two-hit cells in the dermis and that proliferation with
17 Two-hit cells were not detected in the epidermis.
18 location of cells with biallelic mutations ("
two-hit"
cells) was unclear.
19 This work allowed us to identify
two hit compounds with an interesting antitumor mechanis
20 Both EMyT and cilium loss require
two-hit conditions: disassembly/absence of intercellular
21 Among them,
two hit conjugates showed excellent phototherapeutic ind
22 o initiate tumorigenesis through the classic
two-hit CRC pathway.
23 mutants are seen only in trans, suggesting a
two-hit driver event.
24 We employed a
two-hit endotoxemia/pneumonia model, whereby administrat
25 Recently, a '
two-hit'
experimental model of HFpEF was described in wh
26 In this article, we describe
two hit finding approaches leading to the discovery of n
27 Two hits from commercial sources (1, 2) were found activ
28 in vivo activity of hsp110 (CG6603) or tra1,
two hits from the screen, affects neurodegeneration in a
29 A "
two-hit"
genetic model therefore underlies a key phenoty
30 cular and immunohistochemical evidence for a
two-hit (
germline plus somatic) mutation mechanism.
31 The '
two-hit'
group exposed to KA on both P15 and P45 had hig
32 res, and the greater neuronal injury in the '
two-hit'
group.
33 A mouse
two-hit hyperalgesic priming model of migraine was used.
34 Surprisingly, in contrast to Knudsen's
two hit hypothesis, the p.S745L somatic mutation was alw
35 ses for 3p12 markers hence obeying Knudson's
two hit hypothesis.
36 These data support a
two-hit hypothesis as a mechanism of cystogenesis.
37 al mitotic alterations in AD and explain the
two-hit hypothesis by describing how both mechanisms are
38 r initiation of disease, evidence suggests a
two-hit hypothesis for antibody attack on the valve endo
39 In this study, we investigate the
two-hit hypothesis for CCM pathogenesis.
40 ction comprising the second hit of Knudson's
two-hit hypothesis is important in human cancer.
41 Therefore, the
two-hit hypothesis of schizophrenia suggests that MIA co
42 MMR deficiency, the observation expanded the
two-hit hypothesis of tumor suppressor gene loss in canc
43 Knudson's
two-hit hypothesis postulates that genetic alterations i
44 ignant transformation, and suggest Knudson's
two-hit hypothesis should now be expanded to include epi
45 This work provided the foundation for the
two-hit hypothesis that explained the role of recessive
46 ss signalling pathways in AD, we proposed a "
two-hit hypothesis" which states that although either ox
47 The seminal '
two-hit hypothesis' implicitly assumes that bi-allelic t
48 According to Knudson's
two-hit hypothesis, the remaining allele is lost, either
49 Based on the
two-hit hypothesis, we attempted to improve the penetran
50 These findings support a
two-hit hypothesis, whereby cytoplasmic mislocalization
51 IIb activity only, suggesting a noncanonical
two-hit hypothesis.
52 genomic DNA, apparently violating Knudson's
two-hit hypothesis.
53 genetic silencing, thus fulfilling Knudson's
two-hit hypothesis.
54 A "
two-hit"
hypothesis predicts a second somatic hit, in ad
55 ibit embryonic lethality; this supports the "
two-hit"
hypothesis, which proposes that a germline muta
56 lcoholic fatty liver disease (NAFLD) is the "
two-hit"
hypothesis.
57 to metabolic signaling complexes within the '
two hit'
hypothesis, allows schizophrenia to be formulat
58 s and triggering environmental factors (the '
two-hit'
hypothesis).
59 nnot be fully explained by the conventional '
two-hit'
hypothesis, suggesting the existence of inheren
60 causes rather than the long-held Knudson's '
two-hit'
hypothesis; the evidence that retinoma may repr
61 ptibility to ICI-myocarditis, we developed a
two-hit ICI-myocarditis mouse model where cardiac injury
62 uggest a pathologic role of monocytes in the
two-hit (
immune plus neonatal HI) model of neurodevelopm
63 of prenatal, early postnatal, or combined ("
two-hit")
immune activation-on the core behavioral featu
64 Here we use a '
two-hit'
immune-activation paradigm to determine whether
65 IT may be inactivated in accordance with the
two-hit inactivation model, involving deletion of one al
66 that malignant transformation requires full "
two-hit"
inactivation of a tumor-suppressor gene.
67 enes predispose kindreds to HNPCC suggest a "
two-hit"
inactivation of both alleles of a particular MM
68 ealthy volunteer monocytes using an in vitro
two-hit inflammation model.
69 sruption of tight junction integrity after a
two-hit injury with burn and E. faecalis infection, but
70 nst Hsp90 and the subsequent optimization of
two hits into leads with inhibitory activities in the lo
71 d 13 (harboring BRCA2), leading to a double "
two-hit"
involving TP53 and BRCA1/2.
72 Thus, for both L9 and L26 genes, we observe "
two hit"
kinetics commonly observed in genes suppressing
73 the canonical substrate group for PTP1B; the
two hit lists were also very different from each other.
74 variably Rb1(-/-), modeling tumorigenesis by
two-hit loss of RB1 in humans.
75 c inactivation of 1p36 genes in the classic "
two-hit"
manner is scarce; however, many tumor suppresso
76 ns confirm that rhabdomyomas occur through a
two hit mechanism of pathogenesis.
77 in mouse knockout models strongly supports a
two-hit mechanism for cyst formation.
78 n human cancer and typically occur through a
two-hit mechanism involving a missense mutation in one a
79 These results suggest that if a
two-hit mechanism is required for cyst formation in PKD2
80 In keeping with the
two-hit mechanism of cyst formation, approximately 70% o
81 oss-of-function mutations in PRKCSH, and the
two-hit mechanism operational in dominant polycystic kid
82 the malignant transformation of NSCLC via a
two-hit mechanism, including epigenetic changes and alle
83 iguration; this is consistent with a genetic
two-hit mechanism.
84 and produce susceptibility to cancer by the
two-hit mechanism.
85 ic kidney disease, ADPLD may also occur by a
two-hit mechanism.
86 t of benign tumors, hamartomas, occurs via a
two-hit mechanism.
87 or suppressor gene is altered in PNTs by the
two-hit mechanism.
88 ical manifestation of ADPKD also occurs by a
two-hit mechanism.
89 associated with Pkd2 deficiency occurs by a
two-hit mechanism.
90 taneous vascular abnormalities, suggesting a
two-hit mechanism.
91 iency, VMs in HHT are caused by a Knudsonian
two-hit mechanism.
92 tion HHT-related telangiectasia in a genetic
two-hit mechanism.
93 cer genomes are often thought to arise as a "
two-hit"
mechanism in the process of tumor-suppressor ge
94 Our study identifies a potential "
two-hit"
mechanism in which tau acetylation disengages t
95 Our data support a "
two-hit"
mechanism of CTF aggregation dependent on TDP-4
96 lts suggest that (a) RASSF1A inactivation by
two hits (
methylation and loss) is a critical step in SC
97 1 gene usually behave according to Knudson's
two hit model for tumor suppressor genes, seven of eight
98 The results indicate that the "
two hit model" is equally applicable to patients with VH
99 to the view of LIP-driven autoimmunity as a
two hit model; however, not all cofactors have equal abi
100 Our data support a
two-hit model in which the 16p12.1 microdeletion both pr
101 We previously proposed a
two-hit model in which the mouse gastrointestinal Chlamy
102 th variable expressivity indicates that this
two-hit model might be more generally applicable to neur
103 n the presence of amyloid, consistent with a
two-hit model of AD on cognition.
104 s one of the original paradigms of Knudson's
two-hit model of cancer formation, it has become apparen
105 en prion/amyloid disease development and the
two-hit model of cancer progression.
106 ith the unstable Pkd2(WS25) allele suggest a
two-hit model of cystogenesis.
107 These findings challenge the assumed
two-hit model of Emu-Myc lymphoma and demonstrate a func
108 Our findings suggest a
two-hit model of experience-dependent IEG activity and l
109 retch) and thrombin in a previously verified
two-hit model of in vitro ventilator-induced lung injury
110 Finally, informed by this
two-hit model of insomnia and inflammation on depression
111 d neuroinflammation and its relevance to the
two-hit model of schizophrenia.
112 Using a clinically relevant
two-hit model of sepsis, i.e., cecal ligation and punctu
113 The proposed
two-hit model of TRALI is also supported by animal studi
114 view article by Brux and Sachs clarified the
two-hit model of TRALI pathogenesis.
115 We have shown that the
two-hit model requires modification for the APC TSG, bec
116 esis that MIA is a disease primer by using a
two-hit model that combined MIA with a secondary immune
117 ific deletion of Adora2b to ALI, utilizing a
two-hit model where intratracheal LPS treatment is follo
118 Recently, the '
Two-hit model' was used to explain the phenotypic variab
119 According to a
two-hit model, antigen exposure associated with genetic
120 These results suggest a
two-hit model, in which the synergistic induction of bot
121 n ADPKD cyst epithelia in the context of the
two-hit model.
122 enetic predisposition and an immune-mediated
two-hit model.
123 e ASD-like aberrations in mice using a novel
two-hit model.
124 or gain of function, thereby introducing a "
two-hit model." This is highly relevant for cancer resea
125 Consistent with Knudson's "
two hit"
model of tumor suppressor genes, leukemias and
126 The general miRNA patterns followed a "
two-hit"
model as a function of nicotine exposure and ab
127 d within a neurodevelopmental/vulnerability "
two-hit"
model for the etiology of schizophrenia.
128 These data extend the "
two-hit"
model of cystogenesis to include a second focal
129 chemically-modified curcumin (CMC2.24) in a "
two-hit"
model of diabetes-associated periodontitis.
130 We propose a "
two-hit"
model of ER stress-induced cell death involving
131 Taken together these findings implicate a "
two-hit"
model of inflammatory resolution, whereby activ
132 We developed a novel "
two-hit"
model, which combines obesity and insulin resis
133 The '
two-hit'
model is a widely accepted genetic mechanism fo
134 suggests that CCM pathogenesis may follow a
two-hit molecular mechanism, similar to that seen for tu
135 In a
two-hit mouse model of sepsis, we show that tolerance to
136 Testing the
two-hit mouse model should both add new knowledge to the
137 We establish a
two-hit mouse model to study the effect of maternal infl
138 Consistent with this, studies of a "
two-hit"
mouse model of HFpEF confirm that mitochondrial
139 ally, in vivo confirmation was obtained in a
two-hit murine model of VILI where pharmacological inhib
140 Our study established a "
two-hit"
murine model of severe pulmonary hypertension b
141 Secondly, we investigate the
two-hit mutation mechanism for internal organ AVMs, the
142 -associated skin telangiectases develop by a
two-hit mutation mechanism in an HHT gene.
143 ms of CCM have a genetic underpinning of the
two-hit mutation mechanism in the known CCM genes.
144 ns, indicating that CCM follows a Knudsonian
two-hit mutation mechanism.
145 loss of CCM protein staining, supporting the
two-hit mutation mechanism.
146 rine glycine receptor beta subunit gene is a
two-hit mutation, where the hypomorphic alteration in an
147 Therefore,
two "hits,"--
often, but not always, two cleavage events-
148 or cell have been sequentially inactivated ("
two-hit"
oncogenesis mechanism).
149 ce of loss of heterozygosity, the biallelic (
two-hit)
or maximal silencing of LOT1 requires both proc
150 ng through TAS-like genes (TASL), one-hit or
two-hit,
or even two layers of tasiRNA-TASL interactions
151 New data from animal models suggest a
two hit origin of leukemic translocations, where there m
152 Knudson's "
two-hit"
paradigm posits that carcinogenesis requires in
153 form/obliterative arteriopathy induced via a
two-hit pathophysiological mechanism without hypoxia pro
154 In addition, a new example of apparent "
two-hit"
phasiRNA processing was identified.
155 econd, often trivial, stimulus (a so-called "
two hit"
phenomenon).
156 Rb1(+/-) mice incur "
two-hit"
pituitary tumorigenesis; Skp2(-/-);Rb1(+/-) mic
157 Furthermore, in a '
two-hit'
pneumonia model in mice, we have been able to d
158 oncogenic events in such cancers because of
two-hit precursor lesions that have a low probability of
159 ppressor is completely inactivated through a
two-hit process involving a point mutation in one allele
160 Our findings support a
two-hit process of cuprizone-induced demyelination, supp
161 ose that autophagy-mediated cell death is a "
two-hit"
process: Following the cellular stress of the a
162 CoV-2 virus-like particle (VLP) vaccine with
two-hit protection.
163 insufficiency transiently bypasses Knudson's
two-hit requirement could link glycolysis activation by
164 Further characterization of
two hits revealed that the small molecule HDAC inhibitor
165 targets should permit the extension of this "
two-hit"
reverse genetics methodology to other RV genes.
166 Instead neurodegeneration may involve a
two-hit scenario where interference with OPC differentia
167 By conducting a "
two-hit"
screen, we revealed the synergistic reduction o
168 ing a kainic acid (KA)-induced, established '
two-hit'
seizure model in rats.
169 Here, we outline the evolution of the
two hit series to clinical candidates BAY 1161909 and BA
170 stress (CSDS), early life stress (ELS), and
two-hit stress of combined CSDS and ELS were collected.
171 Here we establish a "
two-hit"
stress model in mice wherein stress at a specif
172 ative stress and chelatable iron thus act as
two "hits"
synergistically promoting toxic radical forma
173 throughput screening (HTS) campaign revealed
two hits that were nominated for further optimization st
174 d acute leukaemia is thought to be caused by
two hits,
the first in utero and the second in childhood
175 My analysis supports Knudson's
two-hit theory but is much simpler and easier to underst
176 t for an extra genetic "hit" contradicts the
two-hit theory for the accelerated carcinogenesis associ
177 al microcirculation are in concert with the "
two-hit"
theory for MSOF.
178 clinical scenario has led to the idea of a "
two-hit"
theory for the development of MSOF, the hallmar
179 re located on distinct alleles, resulting in
two hits to ATG7.
180 esis, we optimized the binding affinities of
two hits to the low nanomolar range.
181 somal dominant tumor syndrome resulting from
two hits to the same allele of PLCD1 tumor suppressor ge
182 ), demonstrating for the first time that the
two-hit tumor suppressor gene model applies to the TSC-a
183 plastic complications arise from a classical
two-hit tumor suppressor gene model.
184 solely somatic, mutations in the FH gene, a
two-hit tumor suppressor gene.
185 t in part, by differences in the location of
two-hit tumor suppressor genes across the genome.
186 f clear-cell type (the most common type) are
two-hit tumor suppressor genes, and they cluster in a 43
187 t allele ratios) identified several putative
two-hit tumor suppressor genes, including BAP1.
188 These results support a
two-hit tumor suppressor model for the pathogenesis of S
189 n, implying that ARF can act as a canonical "
two-hit"
tumor suppressor gene.
190 tudies, suggesting that p19ARF is a classic '
two hit'
tumor suppressor.
191 To identify combinations of greater than
two hits,
we used a compressed binary matrix representat
192 Two hits were merged into compound 8 with a 220-380-fold
193 ry of known kinase inhibitors, we identified
two hits with moderate biochemical potencies against GRK
194 As few as one or
two "hits"
with methylglyoxal per protein molecule have