The role of the co-chaperone HOP in plant homeostasis during development and stress.

Proteins need to acquire their native structure in order to become fully functional. In specific cases, the active conformation is obtained spontaneously; nevertheless, many proteins need the assistance of chaperones and co-chaperones to be properly folded. These proteins help to maintain protein homeostasis under control conditions and under different stresses. HOP (HSP70-HSP90 organizing protein) is a highly conserved family of co-chaperones that assist HSP70 and HSP90 in the folding of specific proteins. In the last few years, findings in mammals and yeast have revealed novel functions of HOP and re-defined the role of HOP in protein folding. Here, we provide an overview of the most important aspects of HOP regulation and function in other eukaryotes and analyse whether these aspects are conserved in plants. In addition, we highlight the HOP clients described in plants and the role of HOP in plant development and stress response.

Sex-Related Differences in Heart Failure Diagnosis.

PURPOSE OF REVIEW: The literature on the importance of sex in heart failure diagnosis is scarce. This review aims to summarize current knowledge on sex differences regarding the diagnosis of heart failure. RECENT FINDINGS: Comorbidities are frequent in patients with heart failure, and their prevalence differs between sexes; some differences in symptomatology and diagnostic imaging techniques were also found. Biomarkers also usually show differences between sexes but are not significant enough to establish sex-specific ranges. This article outlines current information related to sex differences in HF diagnosis. Research in this field remains to be done. Maintaining a high diagnostic suspicion, actively searching for the disease, and considering the sex is relevant for early diagnosis and better prognosis. In addition, more studies with equal representation are needed.

High overexpression of CERES, a plant regulator of translation, induces different phenotypical defence responses during TuMV infection.

Mutations in the eukaryotic translation initiation factors eIF4E and eIF(iso)4E confer potyvirus resistance in a range of plant hosts. This supports the notion that, in addition to their role in translation of cellular mRNAs, eIF4E isoforms are also essential for the potyvirus cycle. CERES is a plant eIF4E- and eIF(iso)4E-binding protein that, through its binding to the eIF4Es, modulates translation initiation; however, its possible role in potyvirus resistance is unknown. In this article, we analyse if the ectopic expression of AtCERES is able to interfere with turnip mosaic virus replication in plants. Our results demonstrate that, during infection, the ectopic expression of CERES in Nicotiana benthamiana promotes the development of a mosaic phenotype when it is accumulated to moderate levels, but induces veinal necrosis when it is accumulated to higher levels. This necrotic process resembles a hypersensitive response (HR)-like response that occurs with different HR hallmarks. Remarkably, Arabidopsis plants inoculated with a virus clone that promotes high expression of CERES do not show signs of infection. These final phenotypical outcomes are independent of the capacity of CERES to bind to eIF4E. All these data suggest that CERES, most likely due to its leucine-rich repeat nature, could act as a resistance protein, able to promote a range of different defence responses when it is highly overexpressed from viral constructs.

The co-chaperone HOP3 participates in jasmonic acid signaling by regulating CORONATINE-INSENSITIVE 1 activity.

HOPs (HSP70-HSP90 organizing proteins) are a highly conserved family of HSP70 and HSP90 co-chaperones whose role in assisting the folding of various hormonal receptors has been extensively studied in mammals. In plants, HOPs are mainly associated with stress response, but their potential involvement in hormonal networks remains completely unexplored. In this article we describe that a member of the HOP family, HOP3, is involved in the jasmonic acid (JA) pathway and is linked to plant defense responses not only to pathogens, but also to a generalist herbivore. The JA pathway regulates responses to Botrytis cinerea infection and to Tetranychus urticae feeding; our data demonstrate that the Arabidopsis (Arabidopsis thaliana) hop3-1 mutant shows an increased susceptibility to both. The hop3-1 mutant exhibits reduced sensitivity to JA derivatives in root growth assays and downregulation of different JA-responsive genes in response to methyl jasmonate, further revealing the relevance of HOP3 in the JA pathway. Interestingly, yeast two-hybrid assays and in planta co-immunoprecipitation assays found that HOP3 interacts with COI1, suggesting that COI1 is a target of HOP3. Consistent with this observation, COI1 activity is reduced in the hop3-1 mutant. All these data strongly suggest that, specifically among HOPs, HOP3 plays a relevant role in the JA pathway by regulating COI1 activity in response to JA and, consequently, participating in defense signaling to biotic stresses.

The co-chaperone HOP participates in TIR1 stabilisation and in auxin response in plants.

HOP (HSP70-HSP90 organising protein) is a conserved family of co-chaperones well known in mammals for its role in the folding of signalling proteins associated with development. In plants, HOP proteins have been involved in the response to multiple stresses, but their role in plant development remains elusive. Herein, we describe that the members of the HOP family participate in different aspects of plant development as well as in the response to warm temperatures through the regulation of auxin signalling. Arabidopsis hop1 hop2 hop3 triple mutant shows different auxin-related phenotypes and a reduced auxin sensitivity. HOP interacts with TIR1 auxin coreceptor in vivo. Furthermore, TIR1 accumulation and auxin transcriptional response are reduced in the hop1 hop2 hop3 triple mutant, suggesting that HOP's function in auxin signalling is related, at least, to TIR1 interaction and stabilisation. Interestingly, HOP proteins form part of the same complexes as SGT1b (a different HSP90 co-chaperone) and these co-chaperones synergistically cooperate in auxin signalling. This study provides relevant data about the role of HOP in auxin regulation in plants and uncovers that both co-chaperones, SGT1b and HOP, cooperate in the stabilisation of common targets involved in plant development.

Pressure-Induced Phase Transition and Band Gap Decrease in Semiconducting ß-Cu2V2O7.

The understanding of the interplay between crystal structure and electronic structure in semiconductor materials is of great importance due to their potential technological applications. Pressure is an ideal external control parameter to tune the crystal structures of semiconductor materials in order to investigate their emergent piezo-electrical and optical properties. Accordingly, we investigate here the high-pressure behavior of the semiconducting antiferromagnetic material ß-Cu2V2O7, finding it undergoes a pressure-induced phase transition to γ-Cu2V2O7 below 4000 atm. The pressure-induced structural and electronic evolutions are investigated by single-crystal X-ray diffraction, absorption spectroscopy and ab initio density functional theory calculations. ß-Cu2V2O7 has previously been suggested as a promising photocatalyst for water splitting. Now, these new results suggest that ß-Cu2V2O7 could also be of interest with regards to barocaloric effects, due to the low phase -transition pressure, in particular because it is a multiferroic material. Moreover, the phase transition involves an electronic band gap decrease of approximately 0.2 eV (from 1.93 to 1.75 eV) and a large structural volume collapse of approximately 7%.

High IGKC-Expressing Intratumoral Plasma Cells Predict Response to Immune Checkpoint Blockade.

Resistance to Immune Checkpoint Blockade (ICB) constitutes the current limiting factor for the optimal implementation of this novel therapy, which otherwise demonstrates durable responses with acceptable toxicity scores. This limitation is exacerbated by a lack of robust biomarkers. In this study, we have dissected the basal TME composition at the gene expression and cellular levels that predict response to Nivolumab and prognosis. BCR, TCR and HLA profiling were employed for further characterization of the molecular variables associated with response. The findings were validated using a single-cell RNA-seq data of metastatic melanoma patients treated with ICB, and by multispectral immunofluorescence. Finally, machine learning was employed to construct a prediction algorithm that was validated across eight metastatic melanoma cohorts treated with ICB. Using this strategy, we have unmasked a major role played by basal intratumoral Plasma cells expressing high levels of IGKC in efficacy. IGKC, differentially expressed in good responders, was also identified within the Top response-related BCR clonotypes, together with IGK variants. These results were validated at gene, cellular and protein levels; CD138+ Plasma-like and Plasma cells were more abundant in good responders and correlated with the same RNA-seq-defined fraction. Finally, we generated a 15-gene prediction model that outperformed the current reference score in eight ICB-treated metastatic melanoma cohorts. The evidenced major contribution of basal intratumoral IGKC and Plasma cells in good response and outcome in ICB in metastatic melanoma is a groundbreaking finding in the field beyond the role of T lymphocytes.

Pressure-induced order-disorder transitions in ß-In2S3: an experimental and theoretical study of structural and vibrational properties.

This joint experimental and theoretical study of the structural and vibrational properties of ß-In2S3 upon compression shows that this tetragonal defect spinel undergoes two reversible pressure-induced order-disorder transitions up to 20 GPa. We propose that the first high-pressure phase above 5.0 GPa has the cubic defect spinel structure of α-In2S3 and the second high-pressure phase (ϕ-In2S3) above 10.5 GPa has a defect α-NaFeO2-type (R3̄m) structure. This phase, related to the NaCl structure, has not been previously observed in spinels under compression and is related to both the tetradymite structure of topological insulators and to the defect LiTiO2 phase observed at high pressure in other thiospinels. Structural characterization of the three phases shows that α-In2S3 is softer than ß-In2S3 while ϕ-In2S3 is harder than ß-In2S3. Vibrational characterization of the three phases is also provided, and their Raman-active modes are tentatively assigned. Our work shows that the metastable α phase of In2S3 can be accessed not only by high temperature or varying composition, but also by high pressure. On top of that, the pressure-induced ß-α-ϕ sequence of phase transitions evidences that ß-In2S3, a BIII2XV3 compound with an intriguing structure typical of AIIBIII2XVI4 compounds (intermediate between thiospinels and ordered-vacancy compounds) undergoes: (i) a first phase transition at ambient pressure to a disordered spinel-type structure (α-In2S3), isostructural with those found at high pressure and high temperature in other BIII2XV3 compounds; and (ii) a second phase transition to the defect α-NaFeO2-type structure (ϕ-In2S3), a distorted NaCl-type structure that is related to the defect NaCl phase found at high pressure in AIIBIII2XVI4 ordered-vacancy compounds and to the defect LiTiO2-type phase found at high pressure in AIIBIII2XVI4 thiospinels. This result shows that In2S3 (with its intrinsic vacancies) has a similar pressure behaviour to thiospinels and ordered-vacancy compounds of the AIIBIII2XVI4 family, making ß-In2S3 the union link between such families of compounds and showing that group-13 thiospinels have more in common with ordered-vacancy compounds than with oxospinels and thiospinels with transition metals.

RIMA-Dependent Nuclear Accumulation of IYO Triggers Auxin-Irreversible Cell Differentiation in Arabidopsis.

The transcriptional regulator MINIYO (IYO) is essential and rate-limiting for initiating cell differentiation in Arabidopsis thaliana Moreover, IYO moves from the cytosol into the nucleus in cells at the meristem periphery, possibly triggering their differentiation. However, the genetic mechanisms controlling IYO nuclear accumulation were unknown, and the evidence that increased nuclear IYO levels trigger differentiation remained correlative. Searching for IYO interactors, we identified RPAP2 IYO Mate (RIMA), a homolog of yeast and human proteins linked to nuclear import of selective cargo. Knockdown of RIMA causes delayed onset of cell differentiation, phenocopying the effects of IYO knockdown at the transcriptomic and developmental levels. Moreover, differentiation is completely blocked when IYO and RIMA activities are simultaneously reduced and is synergistically accelerated when IYO and RIMA are concurrently overexpressed, confirming their functional interaction. Indeed, RIMA knockdown reduces the nuclear levels of IYO and prevents its prodifferentiation activity, supporting the conclusion that RIMA-dependent nuclear IYO accumulation triggers cell differentiation in Arabidopsis. Importantly, by analyzing the effect of the IYO/RIMA pathway on xylem pole pericycle cells, we provide compelling evidence reinforcing the view that the capacity for de novo organogenesis and regeneration from mature plant tissues can reside in stem cell reservoirs.

Phase Behavior of TmVO4 under Hydrostatic Compression: An Experimental and Theoretical Study.

We present a structural and optical characterization of magnetoelastic zircon-type TmVO4 at ambient pressure and under high pressure. The properties under high pressure have been determined experimentally under hydrostatic conditions and theoretically using density functional theory. By powder X-ray diffraction we show that TmVO4 undergoes a first-order irreversible phase transition to a scheelite structure above 6 GPa. We have also determined (from powder and single-crystal X-ray diffraction) the bulk moduli of both phases and found that their compressibilities are anisotropic. The band gap of TmVO4 is found to be Eg = 3.7(2) eV. Under compression the band gap opens linearly, until it undergoes a huge collapse following the structural phase transition (ΔEg = 1.15 eV). Ab initio structural and free energy calculations support our findings. Moreover, calculations of the band structure and density of states reveal that for both zircon and scheelite TmVO4 the band gap is entirely determined by the V 3d and O 2p states of the VO43- ion. The behavior of the band gap can thus be understood entirely in terms of the structural modifications of the VO4 units under compression. Additionally, we have calculated the evolution of the infrared and Raman phonons of both phases upon compression. The presence of soft modes is related to the dynamic instability of the low-pressure phase and to the phase transition.

Structural and Lattice-Dynamical Properties of Tb2O3 under Compression: A Comparative Study with Rare Earth and Related Sesquioxides.

We report a joint experimental and theoretical investigation of the high pressure structural and vibrational properties of terbium sesquioxide (Tb2O3). Powder X-ray diffraction and Raman scattering measurements show that cubic Ia3̅ (C-type) Tb2O3 undergoes two phase transitions up to 25 GPa. We observe a first irreversible reconstructive transition to the monoclinic C2/m (B-type) phase at ∼7 GPa and a subsequent reversible displacive transition from the monoclinic to the trigonal P3̅m1 (A-type) phase at ∼12 GPa. Thus, Tb2O3 is found to follow the well-known C → B → A phase transition sequence found in other cubic rare earth sesquioxides with cations of larger atomic mass than Tb. Our ab initio theoretical calculations predict phase transition pressures and bulk moduli for the three phases in rather good agreement with experimental results. Moreover, Raman-active modes of the three phases have been monitored as a function of pressure, while lattice-dynamics calculations have allowed us to confirm the assignment of the experimental phonon modes in the C- and A-type phases as well as to make a tentative assignment of the symmetry of most vibrational modes in the B-type phase. Finally, we extract the bulk moduli and the Raman-active mode frequencies together with their pressure coefficients for the three phases of Tb2O3. These results are thoroughly compared and discussed in relation to those reported for rare earth and other related sesquioxides as well as with new calculations for selected sesquioxides. It is concluded that the evolution of the volume and bulk modulus of all the three phases of these technologically relevant compounds exhibit a nearly linear trend with respect to the third power of the ionic radii of the cations and that the values of the bulk moduli for the three phases depend on the filling of the f orbitals.

Experimental and Theoretical Study of SbPO4 under Compression.

SbPO4 is a complex monoclinic layered material characterized by a strong activity of the nonbonding lone electron pair (LEP) of Sb. The strong cation LEP leads to the formation of layers piled up along the a axis and linked by weak Sb-O electrostatic interactions. In fact, Sb has 4-fold coordination with O similarly to what occurs with the P-O coordination, despite the large difference in ionic radii and electronegativity between both elements. Here we report a joint experimental and theoretical study of the structural and vibrational properties of SbPO4 at high pressure. We show that SbPO4 is not only one of the most compressible phosphates but also one of the most compressible compounds of the ABO4 family. Moreover, it has a considerable anisotropic compression behavior, with the largest compression occurring along a direction close to the a axis and governed by the compression of the LEP and the weak interlayer Sb-O bonds. The strong compression along the a axis leads to a subtle modification of the monoclinic crystal structure above 3 GPa, leading from a 2D to a 3D material. Moreover, the onset of a reversible pressure-induced phase transition is observed above 9 GPa, which is completed above 20 GPa. We propose that the high-pressure phase is a triclinic distortion of the original monoclinic phase. The understanding of the compression mechanism of SbPO4 can aid to improve the ion intercalation and catalytic properties of this layered compound.

Characterization and Decomposition of the Natural van der Waals SnSb2Te4 under Compression.

High pressure X-ray diffraction, Raman scattering, and electrical measurements, together with theoretical calculations, which include the analysis of the topological electron density and electronic localization function, evidence the presence of an isostructural phase transition around 2 GPa, a Fermi resonance around 3.5 GPa, and a pressure-induced decomposition of SnSb2Te4 into the high-pressure phases of its parent binary compounds (α-Sb2Te3 and SnTe) above 7 GPa. The internal polyhedral compressibility, the behavior of the Raman-active modes, the electrical behavior, and the nature of its different bonds under compression have been discussed and compared with their parent binary compounds and with related ternary materials. In this context, the Raman spectrum of SnSb2Te4 exhibits vibrational modes that are associated but forbidden in rocksalt-type SnTe; thus showing a novel way to experimentally observe the forbidden vibrational modes of some compounds. Here, some of the bonds are identified with metavalent bonding, which were already observed in their parent binary compounds. The behavior of SnSb2Te4 is framed within the extended orbital radii map of BA2Te4 compounds, so our results pave the way to understand the pressure behavior and stability ranges of other "natural van der Waals" compounds with similar stoichiometry.

Orpiment under compression: metavalent bonding at high pressure.

We report a joint experimental and theoretical study of the structural, vibrational, and electronic properties of layered monoclinic arsenic sulfide crystals (α-As2S3), aka mineral orpiment, under compression. X-ray diffraction and Raman scattering measurements performed on orpiment samples at high pressure and combined with ab initio calculations have allowed us to determine the equation of state and the tentative assignment of the symmetry of many Raman-active modes of orpiment. From our results, we conclude that no first-order phase transition occurs up to 25 GPa at room temperature; however, compression leads to an isostructural phase transition above 20 GPa. In fact, the As coordination increases from threefold at room pressure to more than fivefold above 20 GPa. This increase in coordination can be understood as the transformation from a solid with covalent bonding to a solid with metavalent bonding at high pressure, which results in a progressive decrease of the electronic and optical bandgap, an increase of the dielectric tensor components and Born effective charges, and a considerable softening of many high-frequency optical modes with increasing pressure. Moreover, we propose that the formation of metavalent bonding at high pressures may also explain the behavior of other group-15 sesquichalcogenides under compression. In fact, our results suggest that group-15 sesquichalcogenides either show metavalent bonding at room pressure or undergo a transition from p-type covalent bonding at room pressure towards metavalent bonding at high pressure, as a precursor towards metallic bonding at very high pressure.

[Mortality associated with fine and coarse suspended particles, in inhabitants of Monterrey Metropolitan Area]. / Mortalidad aguda asociada con partículas suspendidas finas y gruesas en habitantes de la Zona Metropolitana de Monterrey.

OBJECTIVE: To estimate the mortality risk of fine (PM2.5) and coarse (PM2.5-10) particles in the Metropolitan Area of Mon-terrey (MAM). MATERIALS AND METHODS: A retrospective ecological time-series analysis (2000-2014) was conducted using total and specific causes of mortality, and daily mean PM2.5 and PM2.5-10. Generalized additive distributed lag models controlling for trend, seasonality, day of the week, meteoro-logical conditions and gaseous pollutants. RESULTS: Mean (SD) PM2.5 and PM2.5-10 concentrations were 26.59 µg/m3(11.06 µg/m3) and 48.83 µg/m3 (21.15 µg/m3). An increase of 10 µg/m3 of PM2.5 (lag 0) was associated with 11.16% (95%CI:1.03-21.39) increased risk of respiratory mortality in children <=5 years old and 6.6% (95%CI 3.31-9.37) increased risk of pneumonia-influenza in adults >=65 years old. The risk of mortality associated with the concentration of coarse particles was lower. CONCLUSIONS: Positive and significant associations were observed between exposure to particulate matter and daily mortality in the MAM ́s population.

OBJETIVO: Estimar el riesgo de mortalidad asociado con la exposición a partículas finas (PM2.5) y gruesas (PM2.5-10) en la Zona Metropolitana de Monterrey (ZMM). MATERIAL Y MÉTODOS: Estudio ecológico con análisis retrospectivo de series de tiempo (2004-2014) de mortalidad total y especí-fica diaria, y promedio de PM2.5 y PM2.5-10. Modelos aditivos generalizados Poisson con rezagos distribuidos ajustados por tendencia, estacionalidad, día de la semana, condiciones meteorológicas y contaminantes gaseosos. RESULTADOS: 83 (21.15) µg/m3. Cada 10 µg/m3 de aumento de PM2.5 (lag 0) incrementó el riesgo de mortalidad respiratoria en menores de cinco años 11.16% (IC95% 1.03-21.39) y de neumonía e influenza en mayores de 65 años 6.60% (IC95% 3.91-9.37). El riesgo de mortalidad asociado con las PM2.5-10 fue meno. CONCLUSIONES: Se observaron asociaciones positivas y significativas entre exposición a material particulado y la mortalidad diaria en población de la ZMM.

High-Pressure Single-Crystal X-ray Diffraction of Lead Chromate: Structural Determination and Reinterpretation of Electronic and Vibrational Properties.

We have investigated the high-pressure behavior of PbCrO4. In particular, we have probed the existence of structural transitions under high pressure (at 4.5 GPa) by single-crystal X-ray diffraction and density functional theory calculations. The structural sequence of PbCrO4 is different than previously determined. Specifically, we have established that PbCrO4, under pressure, displays a monoclinic-tetragonal phase transition, with no intermediate phases between the low-pressure monoclinic monazite structure (space group P21/ n) and the high-pressure tetragonal structure. The crystal structure of the high-pressure polymorph is, for the first time, undoubtedly determined to a tetragonal scheelite-type structure (space group I41/ a) with unit-cell parameters a = 5.1102(3) Å and c = 12.213(3) Å. These findings have been used for a reinterpretation of previously published Raman and optical-absorption results. Information of calculated infrared-active phonons will be also provided. In addition, the pressure dependence of the unit-cell parameters, atomic positions, bond distances, and polyhedral coordination are discussed. The softest and stiffest direction of compression for monazite-type PbCrO4 are also reported. Finally, the theoretical pressure dependence of infrared-active modes is given, for the first time, for both polymorphs.

Dense Post-Barite-type Polymorph of PbSO4 Anglesite at High Pressures.

Synchrotron X-ray diffraction measurements on lead sulfate have been performed up to 67 GPa using He as pressure transmitting medium. Experiments reveal the existence of a reversible pressure-induced phase transition from the initial Pnma barite-type to the P212121 post-barite-type structure at pressures above 27 GPa. This phase transition involves a volume collapse of 2.4% and requires a considerable pressure overshoot (large pressure range with coexistence of phases) to overcome the large kinetic barrier of the transition. DFT calculations confirm the experimental observations and support the hypothesis that post-barite-type phase is the thermodynamically stable high-pressure structure for ABO4 ternary oxides with large A and small B atoms. The mechanism of the phase transition is described, and the compressibility and anisotropy of both polymorphs are estimated.

Invasive mammal eradication on islands results in substantial conservation gains.

More than US$21 billion is spent annually on biodiversity conservation. Despite their importance for preventing or slowing extinctions and preserving biodiversity, conservation interventions are rarely assessed systematically for their global impact. Islands house a disproportionately higher amount of biodiversity compared with mainlands, much of which is highly threatened with extinction. Indeed, island species make up nearly two-thirds of recent extinctions. Islands therefore are critical targets of conservation. We used an extensive literature and database review paired with expert interviews to estimate the global benefits of an increasingly used conservation action to stem biodiversity loss: eradication of invasive mammals on islands. We found 236 native terrestrial insular faunal species (596 populations) that benefitted through positive demographic and/or distributional responses from 251 eradications of invasive mammals on 181 islands. Seven native species (eight populations) were negatively impacted by invasive mammal eradication. Four threatened species had their International Union for the Conservation of Nature (IUCN) Red List extinction-risk categories reduced as a direct result of invasive mammal eradication, and no species moved to a higher extinction-risk category. We predict that 107 highly threatened birds, mammals, and reptiles on the IUCN Red List-6% of all these highly threatened species-likely have benefitted from invasive mammal eradications on islands. Because monitoring of eradication outcomes is sporadic and limited, the impacts of global eradications are likely greater than we report here. Our results highlight the importance of invasive mammal eradication on islands for protecting the world's most imperiled fauna.

Male breast cancer: correlation between immunohistochemical subtyping and PAM50 intrinsic subtypes, and the subsequent clinical outcomes.

Male breast cancer is a rare disease that is still poorly understood. It is mainly classified by immunohistochemistry as a luminal disease. In this study, we assess for the first time the correlation between molecular subtypes based on a validated six-marker immunohistochemical panel and PAM50 signature in male breast cancer, and the subsequent clinical outcome of these different subtypes. We collected 67 surgical specimens of invasive male breast cancer from four different Spanish pathology laboratories. Immunohistochemical staining for the six-marker panel was performed on tissue microarrays. PAM50 subtypes were determined in a research-use-only nCounter Analysis System. We explored the association of immunohistochemical and PAM50 subtypes. Overall survival and disease-free survival were analyzed in the different subtypes of each classification. The distribution of tumor molecular subtypes according PAM50 was: 60% luminal B, 30% luminal A and 10% human epidermal growth factor receptor 2 (Her2) enriched. Only one Her2-enriched tumor was also positive by immunohistochemistry and was treated with trastuzumab. None of the tumors were basal-like. Using immunohistochemical surrogates, 51% of the tumors were luminal B, 44% luminal A, 4% triple-negative and 1% Her2-positive. The clinicopathological characteristics did not differ significantly between immunohistochemical and PAM50 subtypes. We found a significant worse overall survival in Her2-enriched compared with luminal tumors. Male breast cancer seems to be mainly a genomic luminal disease with a predominance of the luminal B subtype. In addition, we found a proportion of patients with Her2-negative by immunohistochemistry but Her2-enriched profile by PAM50 tumors with a worse outcome compared with luminal subtypes that may benefit from anti-Her2 therapies.

HOP family plays a major role in long-term acquired thermotolerance in Arabidopsis.

HSP70-HSP90 organizing protein (HOP) is a family of cytosolic cochaperones whose molecular role in thermotolerance is quite unknown in eukaryotes and unexplored in plants. In this article, we describe that the three members of the AtHOP family display a different induction pattern under heat, being HOP3 highly regulated during the challenge and the attenuation period. Despite HOP3 is the most heat-regulated member, the analysis of the hop1 hop2 hop3 triple mutant demonstrates that the three HOP proteins act redundantly to promote long-term acquired thermotolerance in Arabidopsis. HOPs interact strongly with HSP90 and part of the bulk of HOPs shuttles from the cytoplasm to the nuclei and to cytoplasmic foci during the challenge. RNAseq analyses demonstrate that, although the expression of the Hsf targets is not generally affected, the transcriptional response to heat is drastically altered during the acclimation period in the hop1 hop2 hop3 triple mutant. This mutant also displays an unusual high accumulation of insoluble and ubiquitinated proteins under heat, which highlights the additional role of HOP in protein quality control. These data reveal that HOP family is involved in different aspects of the response to heat, affecting the plant capacity to acclimate to high temperatures for long periods.