Miracle-dz/UniFAR-FTUs huggingface dataset:
Antipsychotic Behavioral Phenotypes in the Mouse Collaborative Cross Recombinant Inbred Inter-Crosses (RIX)

Schizophrenia is an idiopathic disorder that affects approximately 1% of the human population, and presents with persistent delusions, hallucinations, and disorganized behaviors. Antipsychotics are the standard pharmacological treatment for schizophrenia, but are frequently discontinued by patients due to inefficacy and/or side effects. Chronic treatment with the typical antipsychotic haloperidol causes tardive dyskinesia (TD), which manifests as involuntary and often irreversible orofacial movements in around 30% of patients. Mice treated with haloperidol develop many of the features of TD, including jaw tremors, tongue protrusions, and vacuous chewing movements (VCMs). In this study, we used genetically diverse Collaborative Cross (CC) recombinant inbred inter-cross (RIX) mice to elucidate the genetic basis of antipsychotic-induced adverse drug reactions (ADRs). We performed a battery of behavioral tests in 840 mice from 73 RIX lines (derived from 62 CC strains) treated with haloperidol or placebo in order to monitor the development of ADRs. We used linear mixed models to test for strain and treatment effects. We observed highly significant strain effects for almost all behavioral measurements investigated (p<0.001). Further, we observed strong strain-by-treatment interactions for most phenotypes, particularly for changes in distance traveled, vertical activity, and extrapyramidal symptoms (EPS). Estimates of overall heritability ranged from 0.21 (change in body weight) to 0.4 (VCMs and change in distance traveled) while the portion attributable to the interactions of treatment and strain ranged from 0.01 (for change in body weight) to 0.15 (for change in EPS). Interestingly, close to 30% of RIX mice exhibited VCMs, a sensitivity to haloperidol exposure, approximately similar to the rate of TD in humans chronically exposed to haloperidol. Understanding the genetic basis for the susceptibility to antipsychotic ADRs may be possible in mouse, and extrapolation to humans could lead to safer therapeutic approaches for schizophrenia.
YAP/TAZ Related BioMechano Signal Transduction and Cancer Metastasis

Mechanoreciprocity refers to a cell’s ability to maintain tensional homeostasis in response to various types of forces. Physical forces are continually being exerted upon cells of various tissue types, even those considered static, such as the brain. Through mechanoreceptors, cells sense and subsequently respond to these stimuli. These forces and their respective cellular responses are prevalent in regulating everything from embryogenic tissue-specific differentiation, programmed cell death, and disease progression, the last of which being the subject of extensive attention. Abnormal mechanical remodeling of cells can provide clues as to the pathological status of tissues. This becomes particularly important in cancer cells, where cellular stiffness has been recently accepted as a novel biomarker for cancer metastasis. Several studies have also elucidated the importance of cell stiffness in cancer metastasis, with data highlighting that a reversal of tumor stiffness has the capacity to revert the metastatic properties of cancer. In this review, we summarize our current understanding of extracellular matrix (ECM) homeostasis, which plays a prominent role in tissue mechanics. We also describe pathological disruption of the ECM, and the subsequent implications toward cancer and cancer metastasis. In addition, we highlight the most novel approaches toward understanding the mechanisms which generate pathogenic cell stiffness and provide potential new strategies which have the capacity to advance our understanding of one of human-kinds’ most clinically significant medical pathologies. These new strategies include video-based techniques for structural dynamics, which have shown great potential for identifying full-field, high-resolution modal properties, in this case, as a novel application.
Morphology and SSU rDNA sequences of four cyrtophorian ciliates from China, with description of a new species (Protista, Ciliophora, Phyllopharyngea).

Four cyrtophorian ciliates, Chlamydodon pararoseus sp. n. , Chlamydodon bourlandi Qu et al., 2018, Dysteria crassipes Claparède Lachmann, 1859, and Dysteria monostyla (Ehrenberg, 1838) Kahl, 1931, isolated from coastal waters off China, were investigated using morphological and SSU rDNA sequencing techniques. C. pararoseus sp. n. can be recognized by having a kidney-shaped body, a complete cross-striated band, 44-51 somatic kineties, and 11-14 nematodesmal rods. The other three species were re-described based on new populations. Additionally, the SSU rRNA genes of C. pararoseus sp. n. and D. monostyla were sequenced for the first time. Phylogenetic analyses inferred from SSU rRNA gene sequences reveal that C. pararoseus sp. n. has a close relationship with C. bourlandi and C. mnemosyne Gong et al., 2005 within the genus Chlamydodon; and D. monostyla and D. crassipes cluster with its congeners, which confirms their generic assignments.
Chemical Neurobiology of Progranulin-Deficient Frontotemporal Dementia

Frontotemporal dementia (FTD) is a presenile dementia presenting with a variety of clinical phenotypes arising from Frontotemporal Lobar Degeneration (FTLD), a family of neurodegenrative pathologies with a predeliction for the frontal, insular, and anterior temporal lobes. Known autosomal dominant causes of FTLD include heterozygous mutations in the GRN gene causing haploinsufficiency of progranulin (PGRN) protein. As mRNA from the mutated allele of GRN is degraded via nonsense-mediated mRNA decay mechanisms, one therapeutic avenue for PGRN-deficient FTD is to increase mRNA, and subsequently protein expression, of the ‘wild-type’ (non-mutated) copy of GRN. This dissertation presents the systematic assessment of the abilities of different classes of small molecules to enhance GRN mRNA and PGRN protein expression in human induced pluripotent stem cell (iPSC)-derived neuronal cells. The work explores selectivity and kinetic requirements of histone deacetylase (HDAC) inhibitors to enhance PGRN expression (Chapter 3), defines key epigenetic markers associated with HDAC inhibitor-mediated GRN regulation (Chapter 4), identifies inhibitors of bromodomain and extra-terminal domain containing proteins (BET inhibitors) as a novel class of GRN/PGRN enhancers (Chapter 5), and considers the implications of treatment with other classes of compounds that regulate GRN/PGRN expression (Chapter 6). Finally, the dissertation describes the generation of patient-derived, iPSC models of behavioral variant FTD (bvFTD) using reprogramming technologies that can
A new excised-leaf assay method to test the inoculativity of the Asian citrus psyllid with

The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is the primary vector of Candidatus Liberibacter asiaticus (Las) associated with huanglongbing, or citrus greening, the most devastating citrus (Citrus spp.) disease worldwide. Here, we developed a new "excised-leaf assay" that can speed up Las-inoculativity tests on Asian citrus psyllid from the current 3-12 mo (when using whole citrus seedlings for inoculation) to only 2-3 wk. Young adults of Asian citrus psyllid that had been reared on Las-infected plants were caged on excised healthy sweet orange [Citrus sinensis (L.) Osbeck] leaves for a 1-2-wk inoculation access periods (IAP), and then both psyllids and leaves were tested later by quantitative polymerase chain reaction (PCR). When single adults were tested per leaf, percentages of Las-positive leaves averaged 2-6% by using HLBaspr primers and 10-20% by using the more sensitive LJ900 primers. Higher proportions of Las-positive leaves were obtained with 1) higher densities of inoculating psyllids (5-10 adults per leaf), 2) longer IAPs, and 3) incubation of leaves for 1 wk postinoculation before PCR. Logistic regression analysis indicated a positive correlation between Las titer in Asian citrus psyllid adults tested singly and the probability of detecting Las in the inoculated leaves, correlations that can be very useful in epidemiological studies. Comparison between excised leaves and whole seedlings, inoculated consecutively for 1 wk each by one or a group of psyllids, indicated no significant difference between Las detection in excised leaves or whole plants. This new excised-leaf assay method saves considerable time, materials, and greenhouse space, and it may enhance vector relation and epidemiological studies on Las and potentially other Liberibacter spp. associated with huanglongbing disease.
Genotype distribution and allele frequencies of the genes associated with reproductive traits and hereditary disorders in Japanese native horses

Eight breeds of horse, namely Hokkaido, Kiso, Noma, Taishu, Misaki, Tokara, Miyako, and Yonaguni horses, have currently been conserved as the Japanese native horse. Since to uncover their genetic properties involved in reproductive traits and hereditary disorders is important for their breeding and conservation programs, we investigated genotype distribution and allele frequencies of the genes associated with reproductive traits and hereditary disorders in the populations of the eight Japanese native horse breeds. We genotyped single nucleotide polymorphisms of FKBP6 (g.11040315G>A and g.11040379C>A), CRISP3 (c.622G>A and c.716A>G), and PLCZ1 (g.45586821C>T) genes associated with stallion fertility including semen qualities and impaired acrosome reaction, and found that both desirable and undesirable alleles of FKBP6 and CRISP3 genes are present in the populations, while only undesirable allele of PLCZ1 was observed in these populations. We also genotyped single nucleotide polymorphisms of GYS1 (c.926G>A), RYR1 (c.7360C>G), and SCN4A (c.4248C>G) genes which are associated with polysaccharide storage myopathy, malignant hyperthermia, and hyperkalaemic periodic paralysis, respectively, and found that no mutant alleles responsible for these hereditary disorders are present in the populations of Japanese native horse breeds. These findings will be informative for future breeding and conservation programs for these horse breeds.
β-HPV 8E6 Dysregulates the Hippo Signaling Pathway and Induces Aneuploidy

Beta genus human papillomaviruses (β-HPVs) are associated with cutaneous squamous cell carcinomas (cSCCs) in a subset of immunocompromised patients. Although β-HPVs are not necessary for tumor maintenance, they are hypothesized to destabilize the genome in the early stages of cancer development. Supporting this idea, β-HPV’s 8E6 protein attenuates p53 accumulation after failed cytokinesis. This paper identifies the mechanism of this abatement. We show β-HPV 8E6 dysregulates the Hippo signaling pathway (HP). It increases pro-proliferative gene expression, enhances TEAD activity and promotes cell growth. β-HPV 8E6 also reduces LATS activation and p53-mediated apoptosis following unsuccessful division of mitotic cells. These phenotypes are dependent on β-HPV 8E6 binding and destabilizing a cellular histone acetyltransferase, p300. Despite circumventing apoptosis, β-HPV 8E6 caused increased senescence after unsuccessful cytokinesis. We linked this lack of growth to the viral protein’s inability to prevent cytoplasmic sequestration of the HP transcription factor, YAP. We also show that increased telomerase reverse transcriptase activity (a common alteration in cSCCs) acts synergistically with β-HPV 8E6 to promote cellular proliferation after abortive cytokinesis. While β-HPV 8E6 promoted aneuploidy on its own, this genome destabilization is amplified in cells that do not divide after mitosis. Although our group and others have previously described inhibition of DNA repair, to the best of our knowledge this marks the first time that a β-HPV protein has been connected to chromosome level changes in the cellular genome. This represents a substantial escalation in the known genome destabilizing properties likely to occur during a β-HPV infection. IMPORTANCE There is mounting evidence that β-HPVs contribute to cSCCs development in immunocompromised populations. They may also augment UV’s mutagenic potential, increasing cancer risk in the general population. We demonstrate that β-HPV 8E6 dysregulates the Hippo signaling pathway (HP). HP regulates cell growth and apoptosis in response to a myriad of stimuli, including failed cytokinesis. β-HPV 8E6 attenuates phosphorylation of the HP kinase, LATS, decreasing some but not all downstream signaling events. This allows binucleated cells to avoid apoptosis, however they succumb to senescence. We show that β-HPV 8E6 synergizes with a common cSCC mutation (telomerase activation) to avoid both apoptosis and senescence. We did not find any telomerase immortalized β-HPV 8E6 expressing cells that were not aneuploid after aberrant cytokinesis. This represents a substantial escalation in β-HPV E6’s known mutagenic potential.
Optimasi Proses Produksi Hidrolisat Protein Ikan (Hpi) dari Mujair ( Oreochromis Mossambicus ).

Salah satu upaya untuk meningkatkan nilai tambah ikan bernilai ekonomis rendah adalah dengan memanfaatkannya menjadi hidrolisat protein ikan (HPI). Untuk itu telah dipelajari proses pembuatan HPI dari bahan baku ikan mujair (Oreochromis mossambicus) secara enzimatis. Pada penelitian ini proses hidrolisis dilakukan dengan menambahkan enzim papain kasar (PAYA) yang diperoleh dari pasar lokal ke dalam ikan mujair cacahan dengan konsentrasi 6, 8 dan 10% (b/b). Untuk mempercepat proses hidrolisis, ke dalam campuran ikan dan enzim ditambahkan akuades sebanyak 25% ( b/b ). Inkubasi ilakukan secara aerobik pada suhu 55-­60 derajad Celcius. Pengambilan sampel dilakukan setelah 6 jam, 12 jam, 24 jam, 36 jam, 48 jam, kemudian setiap hari sampai 10 hari lama inkubasi. Analisis dilakukan terhadap produk HPI yang meliputi tingkat pencairan serta rasio antara a‑amino nitrogen dengan total nitrogen dan analisis organoleptik. Hasil percobaan menunjukkan bahwa hidrolisat protein dapat diproduksi dari ikan mujair dengan enzim papain produksi lokal sebanyak 10%, dengan lama hidrolisis 4 hari. Dalam bentuk cair, hidrolisat protein ikan mujair berwarna kuning kecoklatan, berasa gurih, agak manis dan mengandung asam amino yang tidak jauh berbeda dengan kecap ikan maupun sari pati ayam.
Trophic Selective Pressures Organize the Composition of Endolithic Microbial Communities From Global Deserts

Studies of microbial biogeography are often convoluted by extremely high diversity and differences in microenvironmental factors such as pH and nutrient availability. Desert endolithic (inside rock) communities are exceptionally simple ecosystems that can serve as a tractable model for investigating long-range biogeographic effects on microbial communities. We conducted a comprehensive survey of endolithic sandstones using high-throughput marker gene sequencing to characterize global patterns of diversity in endolithic microbial communities. We also tested a range of abiotic variables in order to investigate the factors that drive community assembly at various trophic levels. Macroclimate was found to be the primary driver of endolithic community composition, with the most striking difference witnessed between hot and polar deserts. This difference was largely attributable to the specialization of prokaryotic and eukaryotic primary producers to different climate conditions. On a regional scale, microclimate and properties of the rock substrate were found to influence community assembly, although to a lesser degree than global hot versus polar conditions. We found new evidence that the factors driving endolithic community assembly differ between trophic levels. While phototrophic taxa were rigorously selected for among different sites, heterotrophic taxa were more cosmopolitan, suggesting that stochasticity plays a larger role in heterotroph assembly. This study is the first to uncover the global drivers of desert endolithic diversity using high-throughput sequencing. We demonstrate that phototrophs and heterotrophs in the endolithic community assemble under different stochastic and deterministic influences, emphasizing the need for studies of microorganisms in context of their functional niche in the community.
Reversal versus specialization in floral morphological evolution in Petrocosmea (Gesneriaceae)

A widely held hypothesis in evolution is that adaptive specialization constrains the potential direction of future evolutionary change and thus may be irreversible, also known as Dollo's law. However, this hypothesis has long been subject to debate in evolutionary biology. Floral specialization is intriguing as it is usually linked to reproductive isolation and could affect speciation. Here, following the discovery of four new taxa, we observed some interesting phenomena of reversal versus specialization in morphology in a clade with the most specialized flowers in the genus Petrocosmea. In the phylogenetic tree based on sequences of multiple DNA regions, the morphological reversals, especially the regain of a long corolla tube, are nested within the branches characteristic of normally specialized flowers with a short corolla tube and highly specialized zygomorphy. Our results indicate that the highly specialized floral organ of this clade is still actively evolving in multiple branches toward specialization while reversals to different ancestral states occur in some branches. Great disturbance of ecological environment is likely a crucial factor affecting trait reversibility, such as the rapid uplift of the Himalayan–Tibetan plateau. The four new taxa are treated herein taxonomically. The flowers of this clade represent an interesting model to explore the genetic basis underlying the evolutionary reversal versus specialization and the interplay between genetic factors and environmental variables.
Measuring Genome Sizes Using Read-Depth, k-mers, and Flow Cytometry: Methodological Comparisons in Beetles (Coleoptera)

Measuring genome size across different species can yield important insights into evolution of the genome and allow for more informed decisions when designing next-generation genomic sequencing projects. New techniques for estimating genome size using shallow genomic sequence data have emerged which have the potential to augment our knowledge of genome sizes, yet these methods have only been used in a limited number of empirical studies. In this project, we compare estimation methods using next-generation sequencing (k-mer methods and average read depth of single-copy genes) to measurements from flow cytometry, the gold standard for genome size measures, using ground beetles (Carabidae) and other members of the beetle suborder Adephaga as our test system. We also present a new protocol for using read-depth of single-copy genes to estimate genome size. Additionally, we report flow cytometry measurements for five previously unmeasured carabid species, as well as 21 new draft genomes and six new draft transcriptomes across eight species of adephagan beetles. No single sequence-based method performed well on all species, and all tended to underestimate the genome sizes, although only slightly in most samples. For one species, Bembidion haplogonum, most sequence-based methods yielded estimates half the size suggested by flow cytometry. This discrepancy for k-mer methods can be explained by a large number of repetitive sequences, but we have no explanation for why read-depth methods yielded results that were also strikingly low.
Effect of Different Combinations of Red and Blue LED Light on Growth Characteristics and Pigment Content of In Vitro Tomato Plantlets

The aim of this study was to evaluate the growth characteristics and pigment content of tomato plantlets grown under various ratios of red (R) (661 nm) and blue (B) (449 nm) LED light. In this study, three different ratios of R and B (RB) light such as 5:01, 10:01, and 19:01 along with R (100%) were used. The photosynthetic photon flux density (PPFD), and photoperiod of the growth chamber was 120 ± 5 μmol m−2s−1 and 16/8 h (day/night), respectively. Tomato plantlets were cultured for six weeks in the growth chamber. It was shown that tomato plantlets had higher photosynthesis rate, higher pigments content, higher growth characteristics (e.g., number of leaves, leaf area, shoot number, root number, root length, dry, and fresh mass), and greater surviving rate under the R:B = 10:01 ratio among the treatments. The plantlets showed at least a threefold decrease in photosynthesis rate, as well as a significant abnormal stem elongation when grown under 100% R light. It is concluded that the RB ratio of 10:01 showed excellent performance in all growth parameters. This result has shown that the optimum lighting environment improves tomato plantlet cultures in vitro.
The effect of waiting time on health outcomes and costs of total joint replacement in hip and knee patients

Tuominen U. The effect of waiting time on health outcomes and costs of total joint replacement in hip and knee patients. A prospective randomized controlled trial. Helsinki: The Social Insurance Institution of Finland, Studies in social security and health 126, 2013. 114 pp. ISBN 978-951-669-911-3 (print), ISBN 978-951-669-912-0 (pdf ). Osteoarthritis is the most common cause of musculoskeletal disability and pain. Long waiting times for elective surgery have been a concern in many countries. The aim of this study was to evaluate the effect of waiting time on health outcomes and costs of total joint replacement in hip and knee patients. When placed on the waiting list, patients were randomly allocated to a short waiting time (waiting time ≤ 3 months) or a non-fixed waiting time (waiting time not fixed in advance, patients followed the hospitals’ routine practice) groups. The outcomes were measured by the15D questionnaire, modified Harris Hip and Knee Scores and Visual Analogue Scale. The use and costs of medication, health care and social services were measured. The measurement points were, when placed on the waiting list upon admission, three months and twelve months postoperatively. Quality­ adjusted life years (QALYs) were calculated to evaluate the effect of waiting time on the cost-utility of total joint replacement. The waiting time difference did not result in a significant difference in health outcomes. After surgery, the mean scores of outcomes improved in both randomized groups by a statistically significant margin. The point estimates from cost-utility analyses showed that hip patients in the short waiting time group compared to the non-fixed group gained more QALYs at lower costs, thus suggesting a strong dominance for the shorter waiting time. In knee patients, the situation was the opposite. There were refusals and dropouts during the follow-up, which might introduce bias and uncertainly into the results. There does not seem to be a significant difference between the cost-utility of short and longer waiting times for total joint replacement, at least given the waiting time difference between our study groups. However, due to quite a lot of uncertainty in the results, one has to be cautious about generalizing the findings.