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When people want to conduct a transaction, but doing so would be morally disreputable, they can obfuscate the fact that they are engaging in an exchange while still arranging for a set of transfers that are effectively equivalent to an exchange. Obfuscation through structures such as gift-giving and brokerage is pervasive across a wide range of disreputable exchanges, such as bribery and sex work. In this article, we develop a theoretical account that sheds light on when actors are more versus less likely to obfuscate. Specifically, we report a series of experiments addressing the effect of trust on the decision to engage in obfuscated disreputable exchange. We find that actors obfuscate more often with exchange partners high in loyalty-based trustworthiness, with expected reciprocity and moral discomfort mediating this effect. However, the effect is highly contingent on the type of trust; trust facilitates obfuscation when it is loyalty-based, but this effect flips when trust is ethics-based. Our findings not only offer insights into the important role of relational context in shaping moral understandings and choices about disreputable exchange, but they also contribute to scholarship on trust by demonstrating that distinct forms of trust can have diametrically opposed effects.

Abstract Background Neurosarcoidosis occurs symptomatically in 5–10% of patients with sarcoidosis, and hydrocephalus is a rare complication of neurosarcoidosis, with either acute or subacute onset and presenting symptoms related to increased intracranial pressure. It represents a potentially fatal manifestation with a mortality rate of 22% (increased to 75% in case of coexistence of seizures) that requires a prompt initiation of treatment. High-dose intravenous corticosteroid treatment and neurosurgical treatment must be considered in all cases of neurosarcoidosis hydrocephalus. Case presentation Here we present a case of hydrocephalus in neurosarcoidosis, complicated by generalized seizures, in a 29-year-old Caucasian male patient treated with medical treatment only, with optimal response. Conclusion Since neurosurgery treatment can lead to severe complications, this case report underlines the possibility to undergo only medical treatment in selected cases. Further studies are needed to stratify patients and better identify those eligible for only medical approach.

Abstract Corticobasal syndrome (CBS) is a clinical syndrome determined by various underlying neurodegenerative disorders requiring a pathological assessment for a definitive diagnosis. A literature review was performed following the methodology described in the Cochrane Handbook for Systematic Reviews to investigate the additional value of traditional and cutting-edge cerebrospinal fluid (CSF) and serum/plasma biomarkers in profiling CBS. Four databases were screened applying predefined inclusion criteria: (1) recruiting patients with CBS; (2) analyzing CSF/plasma biomarkers in CBS. The review highlights the potential role of the association of fluid biomarkers in diagnostic workup of CBS, since they may contribute to a more accurate diagnosis and patient selection for future disease-modifying agent; for example, future trial designs should consider baseline CSF Neurofilament Light Chains (NfL) or progranulin dosage to stratify treatment arms according to neuropathological substrates, and serum NfL dosage might be used to monitor the evolution of CBS. In this scenario, prospective cohort studies, starting with neurological examination and neuropsychological tests, should be considered to assess the correlations of clinical profiles and various biomarkers.

This article presents the work of two female students in a rural school who were assigned to respond to a Shakespearean text with a Digital Video (DV) project. The study shows how the teacher provided students appropriate time, mediation, and space in allowing them to bring their out-of-school literacies and interests within an academic context. The students composed a DV interpretation of the "tomorrow and tomorrow and tomorrow" speech from Macbeth. The research examines both the product and process of the students' work. They recursively planned, drafted, and edited as they composed a multimodal response that purposefully attended to the orchestration of visuals, audio, and text. Implications from this study demonstrate the importance of valuing students' identities in classroom settings, emphasizing multiple audiences for student work, highlighting the complexity of compositional decisions students made throughout the entire process of creating their video response, and providing multimodal assessments in academic contexts.

J-domain proteins (JDPs) are obligate cochaperones of Hsp70s. The Class A JDP Apj1 of the yeast cytosol has an unusually complex region between the N-terminal J-domain and the substrate binding region—often called the Grich or GF region in Class A and B JDPs because of its typical abundance of glycine. The N-terminal 161-residue Apj1 fragment is known to be sufficient for Apj1 function in prion curing, driven by the overexpression of Hsp104. Further analyzing the N-terminal segment of Apj1, we found that a 90-residue fragment that includes the 70-residue J-domain and the adjacent 12-residue glutamine/alanine (Q/A) segment is sufficient for curing. Furthermore, the 121-residue fragment that includes the Grich region was sufficient to not only sustain the growth of cells lacking the essential Class B JDP Sis1 but also enabled the maintenance of several prions normally dependent on Sis1 for propagation. A J-domain from another cytosolic JDP could substitute for the Sis1-related functions but not for Apj1 in prion curing. Together, these results separate the functions of JDPs in prion biology and underscore the diverse functionality of multi-domain cytosolic JDPs in yeast.

We present 500 and 700 au resolution 1 and 3 mm Atacama Large Millimeter/submillimeter Array observations, respectively, of protostellar cores in protoclusters Sagittarius B2 (Sgr B2) North (N) and Main (M), parts of the most actively star-forming cloud in our Galaxy. Previous lower-resolution (5000 au) 3 mm observations of this region detected ∼150 sources inferred to be young stellar objects (YSOs) with M > 8 M _⊙ . With a 10-fold increase in resolution, we detect 371 sources at 3 mm and 218 sources in the smaller field of view at 1 mm. The sources seen at low resolution are observed to fragment into an average of two objects. About one-third of the observed sources fragment. Most of the sources we report are marginally resolved and are at least partially optically thick. We determine that the observed sources are most consistent with Stage 0/I YSOs, i.e., rotationally supported disks with an active protostar and an envelope, that are warmer than those observed in the solar neighborhood. We report source-counting-based inferred stellar mass and the star formation rate of the cloud: 2800 M _⊙ and 0.0038 M _⊙ yr ^−1 for Sgr B2 N and 6900 M _⊙ and 0.0093 M _⊙ yr ^−1 for Sgr B2 M, respectively.

We report the discovery of nine new hot molecular cores in the Deep South (DS) region of Sagittarius B2 using Atacama Large Millimeter/submillimeter Array Band 6 observations. We measure the rotational temperature of CH _3 OH and derive the physical conditions present within these cores and the hot core Sgr B2(S). The cores show heterogeneous temperature structure, with peak temperatures between 252 and 662 K. We find that the cores span a range of masses (203–4842 M _⊙ ) and radii (3587–9436 au). CH _3 OH abundances consistently increase with temperature across the sample. Our measurements show the DS hot cores are structurally similar to Galactic disk hot cores, with radii and temperature gradients that are comparable to sources in the disk. They also show shallower density gradients than disk hot cores, which may arise from the Central Molecular Zone’s higher density threshold for star formation. The hot cores have properties which are consistent with those of Sgr B2(N), with three associated with Class II CH _3 OH masers and one associated with an ultra-compact H ii region. Our sample nearly doubles the high-mass star-forming gas mass near Sgr B2(S) and suggests the region may be a younger, comparably massive counterpart to Sgr B2(N) and (M). The relationship between peak CH _3 OH abundance and rotational temperature traced by our sample and a selection of comparable hot cores is qualitatively consistent with predictions from chemical modeling. However, we observe constant peak abundances at higher temperatures ( T ≳ 250 K), which may indicate mechanisms for methanol survival that are not yet accounted for in models.

A wide class of economic exchanges, such as bribery and compensated adoption, are considered morally disreputable precisely because they are seen as economic exchanges. However, parties to these exchanges can structurally obfuscate them by arranging the transfers so as to obscure that a disreputable exchange is occurring at all. In this article, we propose that four obfuscation structures—bundling, brokerage, gift exchange, and pawning—will decrease the moral opprobrium of external audiences by (1) masking intentionality, (2) reducing the explicitness of the reciprocity, and (3) making the exchange appear to be a type of common practice. We report the results from four experiments assessing participants’ moral reactions to scenarios that describe either an appropriate exchange, a quid pro quo disreputable exchange, or various forms of obfuscated exchange. In support of our hypotheses, results show that structural obfuscation effectively mitigates audiences’ moral offense at disreputable exchanges and that the effects are substantially mediated by perceived attributional opacity, transactionalism, and collective validity.

We report the first extragalactic detection of the higher-order millimeter hydrogen recombination lines (Δ n > 2). The γ -, ϵ -, and η -transitions have been detected toward the millimeter continuum source N 105–1 A in the star-forming region N 105 in the Large Magellanic Cloud with the Atacama Large Millimeter/submillimeter Array. We use the H40 α line, the brightest of the detected recombination lines (H40 α , H36 β , H50 β , H41 γ , H57 γ , H49 ϵ , H53 η , and H54 η ), to determine the electron temperature and study ionized gas kinematics in the region, and the 3 mm free–free continuum emission to determine the physical parameters: the size, emission measure, and electron density. We compare the physical properties of N 105–1 A to a large sample of Galactic compact and ultracompact (UC) H ii regions and conclude that N 105–1 A is similar to the most luminous ( L > 10 ^5 L _⊙ ) UC H ii regions in the Galaxy. N 105–1 A is ionized by an O5.5 V star; it is deeply embedded in its natal molecular clump, and likely associated with a (proto)cluster. We incorporate high-resolution molecular line data including CS, SO, SO _2 , and CH _3 OH (∼0.12 pc), and HCO ^+ and CO (∼0.087 pc) to explore the molecular environment of N 105–1 A. Based on the CO data, we find evidence for a cloud–cloud collision that likely triggered star formation in the region. We find no clear outflow signatures, but the presence of filaments and streamers indicates ongoing accretion onto the clump hosting the UC H ii region. Sulfur chemistry in N 105–1 A is consistent with the accretion shock model predictions.

We report first laboratory rest frequencies for rotational transitions of protonated methylamine, CH3NH3+, measured in a cryogenic 22-pole ion trap machine and employing an action spectroscopy scheme. For this prolate symmetric top molecule thirteen transitions between 80 and 240 GHz were detected in the ground vibrational state, covering JK = 2K − 1K up to JK = 6K − 5K with K = 0, 1, 2. Some transitions exhibit noticeable structure that is attributed to internal rotation splitting. As the CN radical and several of its hydrogenated and protonated forms up to methylamine, CH3NH2, are well known entities in the laboratory and in space, protonated methylamine, CH3NH3+, is a promising candidate for future radio astronomical detection.

In adolescents periodontal destruction may be the primary manifestation of an as yet unrecognized rare systemic disease, and it may be up to the periodontist to make the correct tentative diagnosis. Many genetic diseases that present with primary periodontal manifestations in adolescence affect immune function, sometimes with only mild or absent systemic features. They include periodontal Ehlers-Danlos syndrome (lack of attached gingiva, various connective tissue abnormalities), Papillon-Lefèvre syndrome (palmoplantar hyperkeratosis), and plasminogen deficiency (fibrin deposition within mucous membranes). Other immune disorders with severe periodontitis manifesting in adolescence are usually diagnosed in early childhood due to unmistakeable systemic features. They include Cohen syndrome (developmental disorder, truncal obesity, and microcephaly), Hermansky-Pudlak Syndrome (oculocutaneous albinism, bleeding diathesis, and other systemic manifestations), glycogen storage disease type 1b, and Chediak-Higashi syndrome (pyogenic infections, albinism, and neuropathy). The structural integrity of periodontal tissue is affected in genodermatoses such as Kindler syndrome, a type of epidermolysis bullosa. In primary hyperoxaluria, inflammatory periodontal destruction is associated with renal calculi. Breakdown of periodontal tissues independent of dental plaque biofilm-induced periodontitis is found in hypophosphatasia (highly variable skeletal hypomineralization) or isolated odontohypophosphatasia, hypophosphatemic rickets and primary hyperparathyroidism. Finally, alveolar osteolysis mimicking localized periodontitis may be due to neoplastic processes, e.g., in neurofibromatosis type 1 (typical skin features including café au lait macules and neurofibromas), Langerhans cell histiocytosis (locally destructive proliferation of bone marrow-derived immature myeloid dendritic cells), and Gorham-Stout disease (diffuse cystic angiomatosis of bone).

This article examines the economic effects of prizes with implications for the diversity of market positions, especially in cultural fields. Many prizes have three notable features that together yield an emergent reward structure: (1) consumers treat prizes as judgment devices when making purchase decisions, (2) prizes introduce sharp discontinuities between winners and also-rans, and (3) appealing to prize juries requires costly sacrifices of mass audience appeal. When all three conditions obtain, winning a prize is valuable, but seeking it is costly, so trying and failing yields the worst outcome-a logic we characterize as a Tullock lottery. We test the model with analyses of Oscar nominations and Hollywood films from 1985 through 2009. We create an innovative measure of prize-seeking, or "Oscar appeal," on the basis of similarity to recent nominees in terms of such things as genre, plot keywords, and release date. We then show that Oscar appeal has no effect on profitability. However, this zero-order relationship conceals that returns to strong Oscar appeals are bimodal, with super-normal returns for nominees and large losses for snubs. We then argue that the effect of judgment devices on fields depends on how they structure and refract information. © American Sociological Association 2014.

Vaccines and antibody-based therapeutics like convalescent-phase plasma therapy are premised upon inducing or transferring neutralizing antibodies that inhibit SARS-CoV-2 entry into cells. Virus neutralization assays (VNAs) for measuring neutralizing antibody titers (NATs) are an essential part of determining vaccine or therapeutic efficacy.

We present a detailed overview of the science goals and predictions for the Prime-Cam direct-detection camera–spectrometer being constructed by the CCAT-prime collaboration for dedicated use on the Fred Young Submillimeter Telescope (FYST). The FYST is a wide-field, 6 m aperture submillimeter telescope being built (first light in late 2023) by an international consortium of institutions led by Cornell University and sited at more than 5600 m on Cerro Chajnantor in northern Chile. Prime-Cam is one of two instruments planned for FYST and will provide unprecedented spectroscopic and broadband measurement capabilities to address important astrophysical questions ranging from Big Bang cosmology through reionization and the formation of the first galaxies to star formation within our own Milky Way. Prime-Cam on the FYST will have a mapping speed that is over 10 times greater than existing and near-term facilities for high-redshift science and broadband polarimetric imaging at frequencies above 300 GHz. We describe details of the science program enabled by this system and our preliminary survey strategies.

J-domain proteins (JDPs), obligatory Hsp70 cochaperones, play critical roles in protein homeostasis. They promote key allosteric transitions that stabilize Hsp70 interaction with substrate polypeptides upon hydrolysis of its bound ATP. Although a recent crystal structure revealed the physical mode of interaction between a J-domain and an Hsp70, the structural and dynamic consequences of J-domain action once bound and how Hsp70s discriminate among its multiple JDP partners remain enigmatic. We combined free energy simulations, biochemical assays and evolutionary analyses to address these issues. Our results indicate that the invariant aspartate of the J-domain perturbs a conserved intramolecular Hsp70 network of contacts that crosses domains. This perturbation leads to destabilization of the domain-domain interface-thereby promoting the allosteric transition that triggers ATP hydrolysis. While this mechanistic step is driven by conserved residues, evolutionarily variable residues are key to initial JDP/Hsp70 recognition-via electrostatic interactions between oppositely charged surfaces. We speculate that these variable residues allow an Hsp70 to discriminate amongst JDP partners, as many of them have coevolved. Together, our data points to a two-step mode of J-domain action, a recognition stage followed by a mechanistic stage.

Macrophage responses contribute to a diverse array of pathologies ranging from infectious disease to sterile inflammation. Polarization of macrophages determines their cellular function within biological processes. Lipin-1 is a phosphatidic acid phosphatase in which its enzymatic activity contributes to macrophage pro-inflammatory responses. Lipin-1 also possesses transcriptional co-regulator activity and whether this activity is required for macrophage polarization is unknown. Using mice that lack only lipin-1 enzymatic activity or both enzymatic and transcriptional coregulator activities from myeloid cells, we investigated the contribution of lipin-1 transcriptional co-regulator function toward macrophage wound healing polarization. Macrophages lacking both lipin-1 activities did not elicit IL-4 mediated gene expression to levels seen in either wild-type or lipin-1 enzymatically deficient macrophages. Furthermore, mice lacking myeloid-associated lipin-1 have impaired full thickness excisional wound healing compared to wild-type mice or mice only lacking lipin-1 enzymatic activity from myeloid cell. Our study provides evidence that lipin-1 transcriptional co-regulatory activity contributes to macrophage polarization and influences wound healing in vivo.

The role of massive (≥ 8 |$\, {\rm M}_{\odot }$|⁠) stars in defining the energy budget and chemical enrichment of the interstellar medium in their host galaxy is significant. In this first paper from the Tracing Evolution in Massive Protostellar Objects (TEMPO) project we introduce a colour-luminosity selected (L* ∼ 3 × 103 to 1 × 105 L⊙) sample of 38 massive star-forming regions observed with ALMA at 1.3 mm and explore the fragmentation, clustering, and flux density properties of the sample. The TEMPO sample fields are each found to contain multiple fragments (between 2 and 15 per field). The flux density budget is split evenly (53 per cent–47 per cent) between fields where emission is dominated by a single high flux density fragment and those in which the combined flux density of fainter objects dominates. The fragmentation scales observed in most fields are not comparable with the thermal Jeans length, λ J , being larger in the majority of cases, suggestive of some non-thermal mechanism. A tentative evolutionary trend is seen between luminosity of the clump and the 'spectral line richness' of the TEMPO fields; with 6.7 GHz maser associated fields found to be lower luminosity and more line rich. This work also describes a method of line-free continuum channel selection within ALMA data and a generalized approach used to distinguishing sources which are potentially star-forming from those which are not, utilizing interferometric visibility properties. [ABSTRACT FROM AUTHOR]

Silicon-based sensors are widely used for monitoring solar irradiance, in particular, in the field of Photovoltaic (PV) applications. We present a method to correct the global horizontal irradiance measured by silicon-based sensors that reduces the difference to the standard thermopile sensor measurements. A major motivation to use silicon-based sensors for the measurements of irradiance is their lower cost. In addition, their response time is much lower, and their spectral response is much closer to that of the PV systems. The analysis of the differences is based on evaluating four parameters that influence the sensor measurements, namely the temperature, cosine error, spectral mismatch, and calibration factor. Based on the analysis, a correction model is applied to the silicon sensors measurements. The model separates measurements under a clear sky and cloudy sky by combining the clearness index and the solar zenith angle. By applying the correction model on the measurements of the silicon-based sensor, the differences between sensor readings have been reduced significantly. The relative root mean squared difference (rRMSD) between the daily solar irradiation measured by both sensors decreased from 10.6% to 5.4% after applying the correction model, while relative mean absolute difference (rMAD) decreased from 7.4% to 2.5%. The difference in total annual irradiation decreased from 70 KWh/m2 (6.5%) to 15 kWh/m2 (1.5%) by the correction. The presented correction method shows promising results for a further improvement in the accuracy of silicon-based sensors.

Phospholipases are a family of lipid-altering enzymes that can either reduce or increase bioactive lipid levels. Bioactive lipids elicit signaling responses, activate transcription factors, promote G-coupled-protein activity, and modulate membrane fluidity, which mediates cellular function. Phospholipases and the bioactive lipids they produce are important regulators of immune cell activity, dictating both pro-inflammatory and pro-resolving activity. During atherosclerosis, pro-inflammatory and pro-resolving activities govern atherosclerosis progression and regression, respectively. This review will look at the interface of phospholipase activity, immune cell function, and atherosclerosis.

This paper presents an overview of the current status of the Virtual Atomic and Molecular Data Centre (VAMDC) e-infrastructure, including the current status of the VAMDC-connected (or to be connected) databases, updates on the latest technological development within the infrastructure and a presentation of some application tools that make use of the VAMDC e-infrastructure. We analyse the past 10 years of VAMDC development and operation, and assess their impact both on the field of atomic and molecular (A&M) physics itself and on heterogeneous data management in international cooperation. The highly sophisticated VAMDC infrastructure and the related databases developed over this long term make them a perfect resource of sustainable data for future applications in many fields of research. However, we also discuss the current limitations that prevent VAMDC from becoming the main publishing platform and the main source of A&M data for user communities, and present possible solutions under investigation by the consortium. Several user application examples are presented, illustrating the benefits of VAMDC in current research applications, which often need the A&M data from more than one database. Finally, we present our vision for the future of VAMDC.

Context. The G31.41+0.31 Unbiased ALMA sPectral Observational Survey (GUAPOS) project targets the hot molecular core (HMC) G31.41+0.31 (G31) to reveal the complex chemistry of one of the most chemically rich high-mass star-forming regions outside the Galactic center (GC). Aims. In the third paper of the project we present a study of nine O-bearing (CH3OH, 13CH3OH, CH318OH , CH3CHO, CH3OCH3, CH3COCH3, C2H5OH, aGg′-(CH2OH)2, and gGg′-(CH2OH)2) and six N-bearing (CH3CN,13CH3CN, CH313CN, C2H3CN, C2H5CN, and C2H513CN) complex organic molecules toward G31. The aim of this work is to characterize the abundances in G31 and to compare them with the values estimated in other sources. Moreover, we searched for a possible chemical segregation between O-bearing and N-bearing species in G31, which hosts four compact sources as seen with higher angular resolution data. In the discussion we also include the three isomers of C2H4O2 and the O- and N-bearing molecular species NH2CHO, CH3NCO, CH3C(O)CH2, and CH3NHCHO, which were analyzed in previous GUAPOS papers. Methods. Observations were carried out with the interferometer ALMA and cover the entire Band 3 from 84 to 116 GHz (~32 GHz bandwidth) with an angular resolution of 1.2″ × 1.2″ (~4400 au × 4400 au) and a spectral resolution of ~0.488 MHz (~1.3–1.7 km s−1). The transitions of the 14 molecular species were analyzed with the tool SLIM of MADCUBA to determine the physical parameters of the emitting gas. Moreover, we analyzed the morphology of the emission of the molecular species. Results. The values of abundances with respect to H2 in G31 range from 10−6 to 10−10 for the different species. We compared the abundances with respect to methanol of O-bearing, N-bearing, and O- and N-bearing COMs in G31 with 27 other sources, including other hot molecular cores inside and outside the GC, hot corinos, shocked regions, envelopes around young stellar objects, and quiescent molecular clouds, and with chemical models. Conclusions. From the comparison with other sources there is not a unique template for the abundances in hot molecular cores, pointing toward the importance of the thermal history for the chemistry of the various sources. The abundances derived from the chemical models are in good agreement, within a factor of 10, with those of G31. From the analysis of the maps we derived the peak positions of all the molecular species toward G31. Different species peak at slightly different positions, and this, together with the different central velocities of the lines obtained from the spectral fitting, point to chemical differentiation of selected O-bearing species. [ABSTRACT FROM AUTHOR]

Mitochondria play a central role in the biogenesis of iron–sulfur cluster(s) (FeS), protein cofactors needed for many cellular activities. After assembly on scaffold protein Isu, the cluster is transferred onto a recipient apo-protein. Transfer requires Isu interaction with an Hsp70 chaperone system that includes a dedicated J-domain protein co-chaperone (Hsc20). Hsc20 stimulates Hsp70′s ATPase activity, thus stabilizing the critical Isu–Hsp70 interaction. While most eukaryotes utilize a multifunctional mitochondrial (mt)Hsp70, yeast employ another Hsp70 (Ssq1), a product of mtHsp70 gene duplication. Ssq1 became specialized in FeS biogenesis, recapitulating the process in bacteria, where specialized Hsp70 HscA cooperates exclusively with an ortholog of Hsc20. While it is well established that Ssq1 and HscA converged functionally for FeS transfer, whether these two Hsp70s possess similar biochemical properties was not known. Here, we show that overall HscA and Ssq1 biochemical properties are very similar, despite subtle differences being apparent - the ATPase activity of HscA is stimulated to a somewhat higher levels by Isu and Hsc20, while Ssq1 has a higher affinity for Isu and for Hsc20. HscA/Ssq1 are a unique example of biochemical convergence of distantly related Hsp70s, with practical implications, crossover experimental results can be combined, facilitating understanding of the FeS transfer process.

By binding to a multitude of polypeptide substrates, Hsp70-based molecular chaperone systems perform a range of cellular functions. All J-protein co-chaperones play the essential role, via action of their J-domains, of stimulating the ATPase activity of Hsp70, thereby stabilizing its interaction with substrate. In addition, J-proteins drive the functional diversity of Hsp70 chaperone systems through action of regions outside their J-domains. Targeting to specific locations within a cellular compartment and binding of specific substrates for delivery to Hsp70 have been identified as modes of J-protein specialization. To better understand J-protein specialization, we concentrated on Saccharomyces cerevisiae SIS1, which encodes an essential J-protein of the cytosol/nucleus. We selected suppressors that allowed cells lacking SIS1 to form colonies. Substitutions changing single residues in Ydj1, a J-protein, which, like Sis1, partners with Hsp70 Ssa1, were isolated. These gain-of-function substitutions were located at the end of the J-domain, suggesting that suppression was connected to interaction with its partner Hsp70, rather than substrate binding or subcellular localization. Reasoning that, if YDJ1 suppressors affect Ssa1 function, substitutions in Hsp70 itself might also be able to overcome the cellular requirement for Sis1, we carried out a selection for SSA1 suppressor mutations. Suppressing substitutions were isolated that altered sites in Ssa1 affecting the cycle of substrate interaction. Together, our results point to a third, additional means by which J-proteins can drive Hsp70's ability to function in a wide range of cellular processes-modulating the Hsp70-substrate interaction cycle.

We report the discovery of a velocity coherent, funnel-shaped 13CO emission feature in the Galactic centre (GC) using data from the SEDIGISM survey. The molecular cloud appears as a low-velocity structure (VLSR = [ − 3.5,   + 3.5] km s−1) with an angular extent of 0.95° ×1°, extending towards positive Galactic latitudes. The structure is offset from Sgr A* towards negative Galactic longitudes; it spatially and morphologically correlates well with the northern lobe of the 430 pc radio bubble, believed to be the radio counterpart of the multiwavelength GC chimney. Spectral line observations in the frequency range of 85–116 GHz have been carried out using the IRAM 30-m telescope towards 12 positions along the funnel-shaped emission. We examine the 12C/13C isotopic ratios using various molecules and their isotopologues. The mean 12C/13C isotope ratio (30.6 ± 2.9) is consistent with the structure located within inner 3 kpc of the Galaxy and possibly in the GC. The velocity of the molecular funnel is consistent with previous radio recombination line measurements of the northern lobe of radio bubble. Our multiwavelength analysis suggests that the funnel-shaped structure extending over 100 pc above the Galactic plane is the molecular counterpart of the northern GC chimney. [ABSTRACT FROM AUTHOR]

Proteins destined for the mitochondrial matrix are targeted to the inner membrane Tim17/23 translocon by their presequences. Inward movement is driven by the matrix-localized, Hsp70-based motor. The scaffold Tim44, interacting with the matrix face of the translocon, recruits other motor subunits and binds incoming presequence. The basis of these interactions and their functional relationships remains unclear. Using site-specific in vivo crosslinking and genetic approaches in Saccharomyces cerevisiae, we found that both domains of Tim44 interact with the major matrix-exposed loop of Tim23, with the C-terminal domain (CTD) binding Tim17 as well. Results of in vitro experiments showed that the N-terminal domain (NTD) is intrinsically disordered and binds presequence near a region important for interaction with Hsp70 and Tim23. Our data suggest a model in which the CTD serves primarily to anchor Tim44 to the translocon, whereas the NTD is a dynamic arm, interacting with multiple components to drive efficient translocation.